{ "$schema_version": "5.3", "review_mode": "fresh", "claim_restatement": { "index_wording": "Microbiome-driven Obesity Hypothesis", "entry_form": "phenomenon", "gradeable_restatement": "Gut microbial configuration causally drives human fat accumulation through energy harvest, microbial products and endocrine signalling, beyond diet and host physiology.", "restatement_required": true, "split_into": [], "parent_claim": null, "scope_qualifiers": [ { "qualifier": "Species, genotype, baseline disease, diet, dose and timing", "determinable_before_outcome": true, "determined_from": "Enrollment and experimental design, before results; no responder-defined scope.", "action": "retained" } ] }, "hypothesis": { "name": "Microbiome-driven Obesity Hypothesis", "central_claim": "Gut microbial configuration causally drives human fat accumulation through energy harvest, microbial products and endocrine signalling, beyond diet and host physiology.", "proposed_mechanism": "Gut microbial configuration causally drives human fat accumulation through energy harvest, microbial products and endocrine signalling, beyond diet and host physiology.", "claimed_scope": "Human adiposity contribution in prespecified baseline metabolic, sex and dietary contexts; mouse transfer and host-pathway effects scored separately. The registered SC2 asks contribution, not necessary initiation or universal primacy. Weight, fat mass, fat distribution, energy absorption and insulin sensitivity remain distinct outcomes.", "claimed_level": [ "generalization", "progression" ], "is_conjunctive": true, "conjunctive_note": "The index specifies scope-matched human SC2 as the gate. Mouse transfer and human insulin-sensitivity effects are not substituted for human adiposity causation; added SC3 makes that endpoint-transfer claim explicit." }, "rubric_routing": { "primary_rubric": "04-microbiome-systemic.md", "secondary_rubrics": [ "06-metabolism-aging.md" ], "index_notes_applied": [ "The index specifies scope-matched human SC2 as the gate. Mouse transfer and human insulin-sensitivity effects are not substituted for human adiposity causation; added SC3 makes that endpoint-transfer claim explicit." ], "rubric_fit_note": "Exact archived v5.3 framework. Any stale index empirical framing is rechecked against primary results." }, "subclaim_matrix": { "subclaims": [ { "id": "SC1", "statement": "Microbial transfer transmits an adiposity phenotype in defined recipient mice.", "subclaim_type": "mechanism", "scope": "specified donor, diet, housing and germ-free/conventional recipient conditions", "claimed_scope": "specified donor, diet, housing and germ-free/conventional recipient conditions", "governing_rubric": "04-microbiome-systemic.md", "key_evidence_anchor": "Transfer, strain/substrate controls, adiposity and rescue", "hsef_level": "Ζ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Transfer, cultured-community/strain amendment and rescue repeatedly move recipient adiposity, with defined functions and host-receptor tests addressing distinct errors [1-4,6-7,10,12-15,17,28,33-37,41-42,45-49,64,67-68]. The broad defined-recipient claim reaches Ζ across distinct mechanisms; this does not promote every individual strain or infer human causality." }, { "id": "SC2", "statement": "The same microbial mechanism contributes meaningfully to human obesity.", "subclaim_type": "generalization", "scope": "humans with prespecified baseline obesity/metabolic status", "claimed_scope": "humans with prespecified baseline obesity/metabolic status", "governing_rubric": "04-microbiome-systemic.md", "key_evidence_anchor": "Randomized defined microbial/FMT manipulation with adiposity outcomes and diet/engraftment controls", "hsef_level": "Δ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "The Δ crossing rests on a randomized human perturbation with a positive registered primary endpoint in the scoped population: the 2026 pasteurized-Akkermansia weight-maintenance trial [53]. Obese-population strain/formulation trial signals and the randomized FMT fat-distribution contrast add supporting human evidence [9,21,23-25], but GutBugs was null on its BMI-SDS primary and on total body-fat percentage, so its prespecified secondary android/gynoid result, obtained without multiplicity control, supports rather than supplies the crossing. VSL3 high-energy-diet fat-gain attenuation [26] supports human physiology but is outside the registered obese-recipient gate. The 2026 pasteurized-Akk primary weight-maintenance benefit is additional clinical evidence [53], but does not alone establish a living-community or total-fat mechanism. Primary nulls, selected analyses, incomplete mediator attribution and access prevent Ε generalization [5,16,20,22,54-62,65-66]. No universal necessity or primacy burden is imposed on this contributory subclaim." }, { "id": "SC3", "statement": "Microbial effects on insulin sensitivity or inflammation establish that microbes control human body-fat accumulation.", "subclaim_type": "mechanism", "scope": "human intervention populations; adiposity distinct from biomarkers", "claimed_scope": "human intervention populations; adiposity distinct from biomarkers", "governing_rubric": "04-microbiome-systemic.md", "key_evidence_anchor": "Time-ordered adiposity, metabolic and mediator outcomes in the same intervention", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Glucose/insulin and inflammatory effects do not by themselves establish body-fat control. Mouse depletion, human engraftment and clamp interventions can change those readouts without corresponding fat changes [11,14,18-19,38,40,43,52,54-59,63]. Positive fat trials retain their own credit in SC2; metabolic efficacy is not dismissed because complete mediation is absent." } ], "aggregation_rule": "scope-matched", "aggregation_preregistered": true, "aggregation_rationale": "The index specifies scope-matched human SC2 as the gate. Mouse transfer and human insulin-sensitivity effects are not substituted for human adiposity causation; added SC3 makes that endpoint-transfer claim explicit.", "primary_subclaim_id": "SC2", "aggregation_derivation": "The preregistered scope-matched human-contribution gate SC2 yields Δ / Moderate. Selected controlled human adiposity contrasts cross the in-vivo causal boundary, so a blanket Γ on mouse-to-human inference is not reapplied to the convergent human set. SC1 reaches scoped Ζ for animal transmissibility/rescue; SC3 remains Γ for the endpoint-substitution inference. Weakest-link sensitivity is Γ, primary-subclaim and scope-matched Δ. A stronger universal or primary human-driver reading would remain Γ; that is a separate burden, not a requirement silently added to the registered contribution gate.", "aggregation_alternatives": { "weakest_link_would_return": "Γ", "primary_subclaim_would_return": "Δ", "scope_matched_would_return": "Δ", "note": "Separate narrow successes do not replace the preregistered gate." }, "index_rule_deviation": "" }, "competing_models": { "models_evaluated": [ { "rank_in_tournament": 1, "model_id": "M2", "is_nominal": false, "name": "Diet and host energy balance with microbial interaction", "core_claim": "Diet supplies substrate and changes microbial ecology; microbial effects depend on energy exposure and host physiology.", "explains_what_nominal_does_not": "Diet supplies substrate and changes microbial ecology; microbial effects depend on energy exposure and host physiology.", "strongest_supporting_evidence": [ "Diet intervention and matched-diet transfer contrasts, host receptors and diet/strain counterexperiments [2,26,30,34,38-39,51,60,64-65,67-68] map causal interactions." ], "strongest_contradictory_evidence": [ "Diet does not erase microbial contribution: controlled diet plus VSL3 changes fat gain [26], and defined transfer/rescue alters animal adiposity." ], "hsef_level_for_this_model": "Ε", "rationale": "Diet intervention and matched-diet transfer contrasts, host receptors and diet/strain counterexperiments [2,26,30,34,38-39,51,60,64-65,67-68] map causal interactions. Diet does not erase microbial contribution: controlled diet plus VSL3 changes fat gain [26], and defined transfer/rescue alters animal adiposity." }, { "rank_in_tournament": 2, "model_id": "M3", "is_nominal": false, "name": "Metabolic-health modulation with partly independent adiposity", "core_claim": "Microbial interventions can modify insulin, bile or inflammation without a large or consistent body-fat effect.", "explains_what_nominal_does_not": "Microbial interventions can modify insulin, bile or inflammation without a large or consistent body-fat effect.", "strongest_supporting_evidence": [ "Clamp and antibiotic/FMT contrasts with adiposity nulls support endpoint separation [11,14,18-19,54-59,63]." ], "strongest_contradictory_evidence": [ "Selected positive fat or weight-maintenance trials prevent an absolute no-adiposity reading [9,21,23-26,53,65]." ], "hsef_level_for_this_model": "Ε", "rationale": "Clamp and antibiotic/FMT contrasts with adiposity nulls support endpoint separation [11,14,18-19,54-59,63]. Selected positive fat or weight-maintenance trials prevent an absolute no-adiposity reading [9,21,23-26,53,65]." }, { "rank_in_tournament": 3, "model_id": "M1", "is_nominal": true, "name": "Microbial human adiposity contribution", "core_claim": "The registered contributory claim: specific microbial interventions can modify human fat accumulation under bounded conditions.", "explains_what_nominal_does_not": "The registered contributory claim: specific microbial interventions can modify human fat accumulation under bounded conditions.", "strongest_supporting_evidence": [ "Randomized common-diet fat-gain attenuation and selected adiposity contrasts, plus new primary weight maintenance [9,21,23-26,53], cross the human causal boundary." ], "strongest_contradictory_evidence": [ "A universal primary configuration remains Γ: multiple fat/weight-primary nulls, diet dependence, nonliving products and incomplete specificity [5,16,20,22,55,58,61-62,65-66]." ], "hsef_level_for_this_model": "Δ", "rationale": "Randomized common-diet fat-gain attenuation and selected adiposity contrasts, plus new primary weight maintenance [9,21,23-26,53], cross the human causal boundary. A universal primary configuration remains Γ: multiple fat/weight-primary nulls, diet dependence, nonliving products and incomplete specificity [5,16,20,22,55,58,61-62,65-66]." }, { "rank_in_tournament": 4, "model_id": "M4", "is_nominal": false, "name": "Host physiology and reverse direction", "core_claim": "Host genes, pregnancy, medication and energy exposure can remodel microbes before the measured phenotype.", "explains_what_nominal_does_not": "Host genes, pregnancy, medication and energy exposure can remodel microbes before the measured phenotype.", "strongest_supporting_evidence": [ "Host-state mouse contrasts and longitudinal diet/drug observations provide scoped directionality [3-4,10,31,39,41,44,48,50-51,67]." ], "strongest_contradictory_evidence": [ "These effects do not refute forward microbial causality; human observational direction remains partly unresolved." ], "hsef_level_for_this_model": "Ε", "rationale": "Host-state mouse contrasts and longitudinal diet/drug observations provide scoped directionality [3-4,10,31,39,41,44,48,50-51,67]. These effects do not refute forward microbial causality; human observational direction remains partly unresolved." }, { "rank_in_tournament": 5, "model_id": "M5", "is_nominal": false, "name": "Homeostatic compensation", "core_claim": "Microbial calories and signalling can be offset or redirected by appetite, expenditure and absorptive adaptation.", "explains_what_nominal_does_not": "Microbial calories and signalling can be offset or redirected by appetite, expenditure and absorptive adaptation.", "strongest_supporting_evidence": [ "Cold-transfer adaptation and GPR43 substrate signalling demonstrate model compensation [67-68]; protective carbohydrate consumption adds an opposite energy-harvest route [49]." ], "strongest_contradictory_evidence": [ "Human quantitative long-term compensation is not identified by these animal experiments; the model is compatible with some genuine fat effects." ], "hsef_level_for_this_model": "Ε", "rationale": "Cold-transfer adaptation and GPR43 substrate signalling demonstrate model compensation [67-68]; protective carbohydrate consumption adds an opposite energy-harvest route [49]. Human quantitative long-term compensation is not identified by these animal experiments; the model is compatible with some genuine fat effects." } ], "tournament_summary": "Descriptive comparison; does not modify the nominal score. Controlled high-energy feeding with a randomized microbial product [26] separates additional microbial contribution from diet exposure alone; FMT-TRIM [55] shows engraftment can occur without fat or clamp benefit. Those instruments favor interaction and endpoint-specific modulation over either pure co-occurrence or a universal obesity configuration.", "study_separating_rank1_from_rank2": "Controlled high-energy feeding with a randomized microbial product [26] separates additional microbial contribution from diet exposure alone; FMT-TRIM [55] shows engraftment can occur without fat or clamp benefit. Those instruments favor interaction and endpoint-specific modulation over either pure co-occurrence or a universal obesity configuration.", "nominal_wins_only_by_funding_artifact": false, "level_unchanged_by_tournament": true }, "evidence_inventory": [ { "n": 1, "pmid": "17183312", "title": "An obesity-associated gut microbiome with increased capacity for energy harvest.", "citation": "Turnbaugh PJ, Ley RE, Mahowald MA et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006.", "doi": "10.1038/nature05414", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/17183312/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/17183312/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID17183312", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "gnotobiotic mouse transfer", "decisive_perturbation": true, "endogenous": false, "direction": "positive", "what_it_shows": "Obese-donor community transfers greater fat accumulation and energy-harvest capacity to germ-free recipients.", "what_it_does_not_show": "Crude communities and exceptional recipients do not identify a universal human obesity configuration or exclude diet interaction.", "confounders_present": [ "Crude communities and exceptional recipients do not identify a universal human obesity configuration or exclude diet interaction." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 2, "pmid": "24009397", "title": "Gut microbiota from twins discordant for obesity modulate metabolism in mice.", "citation": "Ridaura VK, Faith JJ, Rey FE et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science (New York, N.Y.). 2013.", "doi": "10.1126/science.1241214", "pmcid": "PMC3829625", "url": "https://pubmed.ncbi.nlm.nih.gov/24009397/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24009397/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID24009397", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "gnotobiotic mouse transfer and rescue", "decisive_perturbation": true, "endogenous": false, "direction": "positive", "what_it_shows": "Discordant-twin fecal communities and cultured collections transfer adiposity; lean-community invasion rescues in a diet-dependent manner.", "what_it_does_not_show": "Human donors are not human causal recipients; saturated-fat/low-produce diet blocks rescue and donor/cage dependence limits generality.", "confounders_present": [ "Human donors are not human causal recipients; saturated-fat/low-produce diet blocks rescue and donor/cage dependence limits generality." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 3, "pmid": "25417156", "title": "Human genetics shape the gut microbiome.", "citation": "Goodrich JK, Waters JL, Poole AC et al. Human genetics shape the gut microbiome. Cell. 2014.", "doi": "10.1016/j.cell.2014.09.053", "pmcid": "PMC4255478", "url": "https://pubmed.ncbi.nlm.nih.gov/25417156/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25417156/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID25417156", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "human twin association and defined mouse amendment", "decisive_perturbation": true, "endogenous": false, "direction": "positive", "what_it_shows": "Human heritable Christensenellaceae associate with low BMI; cultured C.minuta amendment reduces recipient mouse weight gain.", "what_it_does_not_show": "Causal attribution applies to mouse amendment; the human twin relation is observational and weight gain is not a human treatment endpoint.", "confounders_present": [ "Causal attribution applies to mouse amendment; the human twin relation is observational and weight gain is not a human treatment endpoint." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 4, "pmid": "28860383", "title": "The intestinal microbiota regulates body composition through NFIL3 and the circadian clock.", "citation": "Wang Y, Kuang Z, Yu X et al. The intestinal microbiota regulates body composition through NFIL3 and the circadian clock. Science (New York, N.Y.). 2017.", "doi": "10.1126/science.aan0677", "pmcid": "PMC5702268", "url": "https://pubmed.ncbi.nlm.nih.gov/28860383/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28860383/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID28860383", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse epithelial pathway manipulation", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "Microbial control of circadian NFIL3 links innate immune signalling to intestinal lipid absorption and body composition.", "what_it_does_not_show": "A host pathway in mice does not demonstrate independent human adiposity causation; circadian and dietary conditions matter.", "confounders_present": [ "A host pathway in mice does not demonstrate independent human adiposity causation; circadian and dietary conditions matter." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 5, "pmid": "39879980", "title": "Akkermansia muciniphila supplementation in patients with overweight/obese type 2 diabetes: Efficacy depends on its baseline levels in the gut.", "citation": "Zhang Y, Liu R, Chen Y et al. Akkermansia muciniphila supplementation in patients with overweight/obese type 2 diabetes: Efficacy depends on its baseline levels in the gut. Cell metabolism. 2025.", "doi": "10.1016/j.cmet.2024.12.010", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/39879980/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39879980/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "Live-Akk-NCT04797442", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "The 58-person live-Akkermansia RCT found no whole-group between-treatment weight or HbA1c difference; low-baseline-Akk subgroup had colonization and fat/weight signals.", "what_it_does_not_show": "Abstract-only subgroup pre-specification, interaction and multiplicity are unresolved; within-arm significance is not a between-arm interaction.", "confounders_present": [ "Abstract-only subgroup pre-specification, interaction and multiplicity are unresolved; within-arm significance is not a between-arm interaction." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 6, "pmid": "15505215", "title": "The gut microbiota as an environmental factor that regulates fat storage.", "citation": "Bäckhed F, Ding H, Wang T et al. The gut microbiota as an environmental factor that regulates fat storage. Proceedings of the National Academy of Sciences of the United States of America. 2004.", "doi": "10.1073/pnas.0407076101", "pmcid": "PMC524219", "url": "https://pubmed.ncbi.nlm.nih.gov/15505215/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/15505215/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID15505215", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse conventionalization and Fiaf genetics", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "Conventionalization increases body fat despite lower intake; Fiaf knockout experiments implicate host lipid-storage regulation.", "what_it_does_not_show": "Germ-free development and host-genotype manipulation limit human inference; later diet/strain counterexperiments constrain universality.", "confounders_present": [ "Germ-free development and host-genotype manipulation limit human inference; later diet/strain counterexperiments constrain universality." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 7, "pmid": "25731162", "title": "Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome.", "citation": "Chassaing B, Koren O, Goodrich JK et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015.", "doi": "10.1038/nature14232", "pmcid": "PMC4910713", "url": "https://pubmed.ncbi.nlm.nih.gov/25731162/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25731162/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID27144359" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID25731162", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "mouse emulsifier exposure and transfer", "decisive_perturbation": true, "endogenous": false, "direction": "positive", "what_it_shows": "Emulsifier-associated communities transfer inflammation/metabolic phenotype; germ-free contrasts support a microbial contribution.", "what_it_does_not_show": "Crude transfer has at most Moderate specificity; exposure may have additional host effects and linked erratum27144359 was not audited in full.", "confounders_present": [ "Crude transfer has at most Moderate specificity; exposure may have additional host effects and linked erratum27144359 was not audited in full." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 8, "pmid": "19043404", "title": "A core gut microbiome in obese and lean twins.", "citation": "Turnbaugh PJ, Hamady M, Yatsunenko T et al. A core gut microbiome in obese and lean twins. Nature. 2009.", "doi": "10.1038/nature07540", "pmcid": "PMC2677729", "url": "https://pubmed.ncbi.nlm.nih.gov/19043404/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/19043404/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID19043404", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human twin-family observational", "decisive_perturbation": false, "endogenous": false, "direction": "positive", "what_it_shows": "154 people show shared microbial gene functions and obesity-associated diversity, phylum and pathway differences.", "what_it_does_not_show": "Families and diet share determinants; association does not establish direction, a diagnostic phylum ratio or a human fat-producing mechanism.", "confounders_present": [ "Families and diet share determinants; association does not establish direction, a diagnostic phylum ratio or a human fat-producing mechanism." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 9, "pmid": "33346848", "title": "Effects of Fecal Microbiome Transfer in Adolescents With Obesity: The Gut Bugs Randomized Controlled Trial.", "citation": "Leong KSW, Jayasinghe TN, Wilson BC et al. Effects of Fecal Microbiome Transfer in Adolescents With Obesity: The Gut Bugs Randomized Controlled Trial. JAMA network open. 2020.", "doi": "10.1001/jamanetworkopen.2020.30415", "pmcid": "PMC7753902", "url": "https://pubmed.ncbi.nlm.nih.gov/33346848/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33346848/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "GutBugs-ACTRN12615001351505", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph1, 1:Methods:paragraph5, 1:Methods:paragraph6, 1:Methods:paragraph7, 1:Methods:paragraph9, 1:Methods:paragraph10, 2:Results:paragraph0, 2:Results:paragraph4, 2:Results:paragraph5, 2:Results:paragraph8. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "GutBugs randomized 87 adolescents: BMI-SDS primary and total-fat percentage null; android/gynoid ratio lower at6/12/26 weeks.", "what_it_does_not_show": "Original Methods use no clinical multiplicity adjustment; secondary fat distribution is not total fat loss, and metabolic-syndrome resolution is post hoc.", "confounders_present": [ "Original Methods use no clinical multiplicity adjustment; secondary fat distribution is not total fat loss, and metabolic-syndrome resolution is post hoc." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 10, "pmid": "31604271", "title": "The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3.", "citation": "Kuang Z, Wang Y, Li Y et al. The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3. Science (New York, N.Y.). 2019.", "doi": "10.1126/science.aaw3134", "pmcid": "PMC7158748", "url": "https://pubmed.ncbi.nlm.nih.gov/31604271/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31604271/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID31604271", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse epithelial HDAC3 manipulation", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "Epithelial HDAC3 integrates microbial/circadian cues, induces Cd36/lipid uptake and promotes diet-induced obesity.", "what_it_does_not_show": "Host transcriptional perturbation supports a mouse mechanism; human adiposity and effect magnitude were not established.", "confounders_present": [ "Host transcriptional perturbation supports a mouse mechanism; human adiposity and effect magnitude were not established." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 11, "pmid": "22728514", "title": "Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome.", "citation": "Vrieze A, Van Nood E, Holleman F et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012.", "doi": "10.1053/j.gastro.2012.06.031", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/22728514/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/22728514/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "ErratumIn: PMID not supplied" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "Lean-FMT-NTR1776", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "Randomized lean versus autologous FMT improved six-week clamp insulin sensitivity in metabolic-syndrome men.", "what_it_does_not_show": "Insulin sensitivity is not fat accumulation; crude FMT lacks strain attribution and the linked unspecified erratum requires separate audit.", "confounders_present": [ "Insulin sensitivity is not fat accumulation; crude FMT lacks strain attribution and the linked unspecified erratum requires separate audit." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 12, "pmid": "41197631", "title": "Dietary fat disrupts a commensal-host lipid network that promotes metabolic health.", "citation": "Klag K, Ott D, Tippetts TS et al. Dietary fat disrupts a commensal-host lipid network that promotes metabolic health. Cell metabolism. 2026.", "doi": "10.1016/j.cmet.2025.10.007", "pmcid": "PMC12717881", "url": "https://pubmed.ncbi.nlm.nih.gov/41197631/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41197631/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID41197631", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "defined mouse microbe and purified-lipid perturbation", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "Turicibacter and purified bacterial lipids suppress host ceramides/fat uptake and obesity; dietary fat reduces colonization and continuous dosing restores benefit.", "what_it_does_not_show": "The human metagenomic relation is observational; diet-dependent microbial protection does not establish a human pro-obesity configuration.", "confounders_present": [ "The human metagenomic relation is observational; diet-dependent microbial protection does not establish a human pro-obesity configuration." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 13, "pmid": "29649441", "title": "Small Intestine Microbiota Regulate Host Digestive and Absorptive Adaptive Responses to Dietary Lipids.", "citation": "Martinez-Guryn K, Hubert N, Frazier K et al. Small Intestine Microbiota Regulate Host Digestive and Absorptive Adaptive Responses to Dietary Lipids. Cell host & microbe. 2018.", "doi": "10.1016/j.chom.2018.03.011", "pmcid": "PMC5912695", "url": "https://pubmed.ncbi.nlm.nih.gov/29649441/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29649441/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID29649441", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "mouse jejunal transfer and organoids", "decisive_perturbation": true, "endogenous": false, "direction": "positive", "what_it_shows": "Jejunal microbiota from high-fat donors increases recipient lipid absorption even on low-fat diet; conditioned media induce epithelial uptake genes.", "what_it_does_not_show": "Recipient absorption and organoid activity are not a quantified human body-fat effect; crude transfer specificity remains limited.", "confounders_present": [ "Recipient absorption and organoid activity are not a quantified human body-fat effect; crude transfer specificity remains limited." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 14, "pmid": "30030441", "title": "Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism.", "citation": "Zarrinpar A, Chaix A, Xu ZZ et al. Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism. Nature communications. 2018.", "doi": "10.1038/s41467-018-05336-9", "pmcid": "PMC6054678", "url": "https://pubmed.ncbi.nlm.nih.gov/30030441/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30030441/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID30030441", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "mouse antibiotic depletion", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Depletion improves glucose tolerance and insulin sensitivity without changing adiposity, alongside SCFA/bile changes.", "what_it_does_not_show": "Broad antibiotics have host effects; glucose improvement explicitly cannot substitute for fat loss.", "confounders_present": [ "Broad antibiotics have host effects; glucose improvement explicitly cannot substitute for fat loss." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 15, "pmid": "26740296", "title": "Microbiota-induced obesity requires farnesoid X receptor.", "citation": "Parséus A, Sommer N, Sommer F et al. Microbiota-induced obesity requires farnesoid X receptor. Gut. 2017.", "doi": "10.1136/gutjnl-2015-310283", "pmcid": "PMC5534765", "url": "https://pubmed.ncbi.nlm.nih.gov/26740296/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26740296/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID26740296", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse FXR genetics and transfer", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "FXR genotype and germ-free/conventional contrasts change diet-induced adiposity; donor community transfers phenotype.", "what_it_does_not_show": "Host receptor dependence and transfer do not locate an invariant microbial cause of human obesity.", "confounders_present": [ "Host receptor dependence and transfer do not locate an invariant microbial cause of human obesity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 16, "pmid": "31263284", "title": "Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study.", "citation": "Depommier C, Everard A, Druart C et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nature medicine. 2019.", "doi": "10.1038/s41591-019-0495-2", "pmcid": "PMC6699990", "url": "https://pubmed.ncbi.nlm.nih.gov/31263284/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31263284/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "Akk-NCT02637115", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 0:Online Methods:paragraph0, 0:Online Methods:paragraph1, 0:Online Methods:paragraph2, 0:Online Methods:paragraph4, 0:Online Methods:paragraph5, 0:Online Methods:paragraph6, 0:Online Methods:paragraph13, 0:Online Methods:paragraph15, 7:Main text (unsectioned body paragraphs):paragraph1, 7:Main text (unsectioned body paragraphs):paragraph2, 7:Main text (unsectioned body paragraphs):paragraph3, 7:Main text (unsectioned body paragraphs):paragraph13, 7:Main text (unsectioned body paragraphs):paragraph14, 7:Main text (unsectioned body paragraphs):paragraph4, 7:Main text (unsectioned body paragraphs):paragraph5, 7:Main text (unsectioned body paragraphs):paragraph6, 7:Main text (unsectioned body paragraphs):paragraph7, 7:Main text (unsectioned body paragraphs):paragraph8, 7:Main text (unsectioned body paragraphs):paragraph9. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "2019 live/pasteurized Akk pilot improved selected metabolic measures;40enrolled32 completed; weight/fat changes were nonsignificant nearP=.09.", "what_it_does_not_show": "Body fat used bioimpedance, not DXA; original text and abstract differ on the fat comparator, but neither demonstrates significant fat loss; calorie/activity detail and baseline insulin balance limited.", "confounders_present": [ "Body fat used bioimpedance, not DXA; original text and abstract differ on the fat comparator, but neither demonstrates significant fat loss; calorie/activity detail and baseline insulin balance limited." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 17, "pmid": "27892954", "title": "A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice.", "citation": "Plovier H, Everard A, Druart C et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nature medicine. 2017.", "doi": "10.1038/nm.4236", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/27892954/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/27892954/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "Akk-preliminary-human-overlaps-NCT02637115-plus-mouse", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "defined mouse bacterium and protein perturbation", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "Pasteurization and Amuc1100/TLR2-linked protein partly recapitulate metabolic/fat benefits in mice; preliminary human safety was reported.", "what_it_does_not_show": "A bioactive nonliving component is not living-community engraftment; preliminary human volunteers belong to the later2019trial family.", "confounders_present": [ "A bioactive nonliving component is not living-community engraftment; preliminary human volunteers belong to the later2019trial family." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 18, "pmid": "31301451", "title": "Effects of Fecal Microbiota Transplantation With Oral Capsules in Obese Patients.", "citation": "Allegretti JR, Kassam Z, Mullish BH et al. Effects of Fecal Microbiota Transplantation With Oral Capsules in Obese Patients. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2020.", "doi": "10.1016/j.cgh.2019.07.006", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/31301451/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31301451/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "Allegretti-FMT-NCT02741518", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Obese metabolically uncompromised participants show donor-like engraftment/bile changes but no GLP1-area or BMI improvement.", "what_it_does_not_show": "Safety was primary, small pilot; PubMed abstract has an implausible BMI-threshold typo, so exact eligibility needs original verification.", "confounders_present": [ "Safety was primary, small pilot; PubMed abstract has an implausible BMI-threshold typo, so exact eligibility needs original verification." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 19, "pmid": "33785557", "title": "Microbiota engraftment after faecal microbiota transplantation in obese subjects with type 2 diabetes: a 24-week, double-blind, randomised controlled trial.", "citation": "Ng SC, Xu Z, Mak JWY et al. Microbiota engraftment after faecal microbiota transplantation in obese subjects with type 2 diabetes: a 24-week, double-blind, randomised controlled trial. Gut. 2022.", "doi": "10.1136/gutjnl-2020-323617", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33785557/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33785557/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "Repeated-FMT-NCT03127696", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "Repeated FMT in 61 obese T2D adults improved24 week donor engraftment, the primary endpoint; combined lifestyle arm had lipid/liver-stiffness changes.", "what_it_does_not_show": "Engraftment-primary success is not adiposity success; baseline comparisons and cointervention cannot establish independent FMT fat loss.", "confounders_present": [ "Engraftment-primary success is not adiposity success; baseline comparisons and cointervention cannot establish independent FMT fat loss." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 20, "pmid": "31952249", "title": "Effects of Synbiotic Supplement on Human Gut Microbiota, Body Composition and Weight Loss in Obesity.", "citation": "Sergeev IN, Aljutaily T, Walton G et al. Effects of Synbiotic Supplement on Human Gut Microbiota, Body Composition and Weight Loss in Obesity. Nutrients. 2020.", "doi": "10.3390/nu12010222", "pmcid": "PMC7019807", "url": "https://pubmed.ncbi.nlm.nih.gov/31952249/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31952249/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID31952249", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "negative", "what_it_shows": "Twenty-person synbiotic plus reduced-energy diet pilot changed beneficial taxa but not between-arm body mass, fat mass or composition.", "what_it_does_not_show": "Small precision and combined diet limit exclusion of modest effects; taxa improvement is not a successful obesity endpoint.", "confounders_present": [ "Small precision and combined diet limit exclusion of modest effects; taxa improvement is not a successful obesity endpoint." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 21, "pmid": "30262813", "title": "Effects of daily consumption of the probiotic Bifidobacterium animalis subsp. lactis CECT 8145 on anthropometric adiposity biomarkers in abdominally obese subjects: a randomized controlled trial.", "citation": "Pedret A, Valls RM, Calderón-Pérez L et al. Effects of daily consumption of the probiotic Bifidobacterium animalis subsp. lactis CECT 8145 on anthropometric adiposity biomarkers in abdominally obese subjects: a randomized controlled trial. International journal of obesity (2005). 2019.", "doi": "10.1038/s41366-018-0220-0", "pmcid": "PMC6760601", "url": "https://pubmed.ncbi.nlm.nih.gov/30262813/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30262813/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID30262813", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Methods, 2:Results. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "Ba8145 original Methods/Results report live-cell BMI and killed-cell waist-related between-placebo benefits;126 received intervention of 135 reported participants.", "what_it_does_not_show": "MRI visceral-fat between-placebo contrasts are nonsignificant(P=.120/.086 for killed cells), despite significant within-baseline change; statistics/hierarchy in unread supplement and higher killed-arm fiber complicate interpretation; Akk correlation is not mediation.", "confounders_present": [ "MRI visceral-fat between-placebo contrasts are nonsignificant(P=.120/.086 for killed cells), despite significant within-baseline change; statistics/hierarchy in unread supplement and higher killed-arm fiber complicate interpretation; Akk correlation is not mediation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 22, "pmid": "27810310", "title": "Probiotic With or Without Fiber Controls Body Fat Mass, Associated With Serum Zonulin, in Overweight and Obese Adults-Randomized Controlled Trial.", "citation": "Stenman LK, Lehtinen MJ, Meland N et al. Probiotic With or Without Fiber Controls Body Fat Mass, Associated With Serum Zonulin, in Overweight and Obese Adults-Randomized Controlled Trial. EBioMedicine. 2016.", "doi": "10.1016/j.ebiom.2016.10.036", "pmcid": "PMC5264483", "url": "https://pubmed.ncbi.nlm.nih.gov/27810310/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/27810310/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "B420-NCT01978691", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Materials and Methods:paragraph0, 1:Materials and Methods:paragraph5, 1:Materials and Methods:paragraph7, 1:Materials and Methods:paragraph15, 1:Materials and Methods:paragraph16, 1:Materials and Methods:paragraph17, 2:Results:paragraph0, 2:Results:paragraph1, 2:Results:paragraph4, 2:Results:paragraph5, 2:Results:paragraph7, 2:Results:paragraph10. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "B420factorial RCT randomized 225; ITT 209 fat-primary null; PP combination and post-unblinding factorial analyses positive.", "what_it_does_not_show": "Original Methods confirm modified ITT/LOCF, Dunnett contrasts and posthoc PP factorial; selective compliance and reduced intake weaken direct microbial mediation; zonulin correlation is not barrier causation.", "confounders_present": [ "Original Methods confirm modified ITT/LOCF, Dunnett contrasts and posthoc PP factorial; selective compliance and reduced intake weaken direct microbial mediation; zonulin correlation is not barrier causation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 23, "pmid": "39456659", "title": "Gut Microbiome and Metabolome Alterations in Overweight or Obese Adult Population after Weight-Loss Bifidobacterium breve BBr60 Intervention: A Randomized Controlled Trial.", "citation": "Bai Z, Wu Y, Gao D et al. Gut Microbiome and Metabolome Alterations in Overweight or Obese Adult Population after Weight-Loss Bifidobacterium breve BBr60 Intervention: A Randomized Controlled Trial. International journal of molecular sciences. 2024.", "doi": "10.3390/ijms252010871", "pmcid": "PMC11507383", "url": "https://pubmed.ncbi.nlm.nih.gov/39456659/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39456659/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID39456659", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "75-person BBr60 plus common dietary guidance trial reports greater weight/BMI reduction and metabolic/taxa changes than placebo.", "what_it_does_not_show": "Abstract-only fat outcomes, primary hierarchy and multiplicity remain unresolved; metabolomic correlation does not identify the mediator.", "confounders_present": [ "Abstract-only fat outcomes, primary hierarchy and multiplicity remain unresolved; metabolomic correlation does not identify the mediator." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 24, "pmid": "24299712", "title": "Effect of Lactobacillus rhamnosus CGMCC1.3724 supplementation on weight loss and maintenance in obese men and women.", "citation": "Sanchez M, Darimont C, Drapeau V et al. Effect of Lactobacillus rhamnosus CGMCC1.3724 supplementation on weight loss and maintenance in obese men and women. The British journal of nutrition. 2014.", "doi": "10.1017/S0007114513003875", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/24299712/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24299712/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID24299712", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "L.rhamnosus formulation with prebiotics had an overall ITT weight null but treatment-by-sex interaction; women showed more weight/fat loss over24 weeks.", "what_it_does_not_show": "Sex interaction retains scoped causal credit; formulation and restricted diet prevent isolating a strain-only mechanism, and sex-specific primary status remains to be audited.", "confounders_present": [ "Sex interaction retains scoped causal credit; formulation and restricted diet prevent isolating a strain-only mechanism, and sex-specific primary status remains to be audited." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 25, "pmid": "40877311", "title": "Long-term health outcomes in adolescents with obesity treated with faecal microbiota transplantation: 4-year follow-up.", "citation": "Wilson BC, Zuppi M, Derraik JGB et al. Long-term health outcomes in adolescents with obesity treated with faecal microbiota transplantation: 4-year follow-up. Nature communications. 2025.", "doi": "10.1038/s41467-025-62752-4", "pmcid": "PMC12394558", "url": "https://pubmed.ncbi.nlm.nih.gov/40877311/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40877311/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "GutBugs-ACTRN12615001351505", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph0, 1:Results:paragraph1, 1:Results:paragraph2, 1:Results:paragraph3, 1:Results:paragraph4, 1:Results:paragraph5, 1:Results:paragraph6, 1:Results:paragraph8, 1:Results:paragraph10, 1:Results:paragraph12, 1:Results:paragraph14, 1:Results:paragraph15, 2:Discussion:paragraph1, 2:Discussion:paragraph3, 3:Methods:paragraph0, 3:Methods:paragraph1, 3:Methods:paragraph2, 3:Methods:paragraph3, 3:Methods:paragraph17, 3:Methods:paragraph42, 3:Methods:paragraph43, 3:Methods:paragraph45, 3:Methods:paragraph46. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human randomized-cohort follow-up", "decisive_perturbation": true, "endogenous": false, "direction": "mixed", "what_it_shows": "2025GutBugs4 year follow-up found lower waist and body-fat percentage among 55returnees, with persistent donor strains and nonsignificant BMI difference.", "what_it_does_not_show": "Same trial family; unblinded after26 weeks,37%lost, no missing-data imputation and unadjusted clinical multiplicity; intervening diet/medication unknown.", "confounders_present": [ "Same trial family; unblinded after26 weeks,37%lost, no missing-data imputation and unadjusted clinical multiplicity; intervening diet/medication unknown." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 26, "pmid": "26466123", "title": "Probiotic supplementation attenuates increases in body mass and fat mass during high-fat diet in healthy young adults.", "citation": "Osterberg KL, Boutagy NE, McMillan RP et al. Probiotic supplementation attenuates increases in body mass and fat mass during high-fat diet in healthy young adults. Obesity (Silver Spring, Md.). 2015.", "doi": "10.1002/oby.21230", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/26466123/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26466123/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID26466123", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "20healthy young men on a common high-fat1000 kcal-surplus diet gained less DXA fat and weight with VSL3 than placebo after4 weeks.", "what_it_does_not_show": "Direct controlled fat-accumulation contrast supports a bounded human contribution; small/short study, multiple-strain product and unverified engraftment limit mechanism/generalization.", "confounders_present": [ "Direct controlled fat-accumulation contrast supports a bounded human contribution; small/short study, multiple-strain product and unverified engraftment limit mechanism/generalization." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 27, "pmid": "33432175", "title": "Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals.", "citation": "Asnicar F, Berry SE, Valdes AM et al. Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals. Nature medicine. 2021.", "doi": "10.1038/s41591-020-01183-8", "pmcid": "PMC8353542", "url": "https://pubmed.ncbi.nlm.nih.gov/33432175/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33432175/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID33432175", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human deeply phenotyped observational", "decisive_perturbation": false, "endogenous": false, "direction": "positive", "what_it_shows": "PREDICT1 links microbiome, habitual diet and standardized-meal metabolic responses in 1098 participants with external biomarker replication.", "what_it_does_not_show": "Same-meal responses and prediction are not microbiome randomization; public cohorts may recur elsewhere and cannot become independent causal replications.", "confounders_present": [ "Same-meal responses and prediction are not microbiome randomization; public cohorts may recur elsewhere and cannot become independent causal replications." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 28, "pmid": "38996548", "title": "Obesity-enriched gut microbe degrades myo-inositol and promotes lipid absorption.", "citation": "Wu C, Yang F, Zhong H et al. Obesity-enriched gut microbe degrades myo-inositol and promotes lipid absorption. Cell host & microbe. 2024.", "doi": "10.1016/j.chom.2024.06.012", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38996548/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38996548/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID38996548", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "human association and defined mouse gene/strain perturbation", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "631obese374control cohort associates Megamonas with obesity; M.rupellensis and heterologous iolG expression promote mouse lipid absorption, with myo-inositol functional support.", "what_it_does_not_show": "The human portion is observational and the primary body unavailable; gene/strain perturbations narrow a mouse mechanism without demonstrating human treatment mediation.", "confounders_present": [ "The human portion is observational and the primary body unavailable; gene/strain perturbations narrow a mouse mechanism without demonstrating human treatment mediation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 29, "pmid": "30388453", "title": "US Immigration Westernizes the Human Gut Microbiome.", "citation": "Vangay P, Johnson AJ, Ward TL et al. US Immigration Westernizes the Human Gut Microbiome. Cell. 2018.", "doi": "10.1016/j.cell.2018.10.029", "pmcid": "PMC6498444", "url": "https://pubmed.ncbi.nlm.nih.gov/30388453/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30388453/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID30388453", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human immigration longitudinal observational", "decisive_perturbation": false, "endogenous": false, "direction": "positive", "what_it_shows": "Immigration-associated microbial loss and Westernization track residence, generation and obesity, including19 people sampled before/after migration.", "what_it_does_not_show": "Migration simultaneously changes food, environment and host exposures; longitudinal association does not isolate microbial causation of fat gain.", "confounders_present": [ "Migration simultaneously changes food, environment and host exposures; longitudinal association does not isolate microbial causation of fat gain." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 30, "pmid": "32075887", "title": "Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake.", "citation": "Meslier V, Laiola M, Roager HM et al. Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake. Gut. 2020.", "doi": "10.1136/gutjnl-2019-320438", "pmcid": "PMC7306983", "url": "https://pubmed.ncbi.nlm.nih.gov/32075887/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32075887/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID32075887", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human dietary randomized intervention", "decisive_perturbation": false, "endogenous": false, "direction": "positive", "what_it_shows": "Isocaloric Mediterranean diet altered microbes/metabolites and lowered cholesterol, the primary endpoint, in 82adults.", "what_it_does_not_show": "Diet was randomized, not microbes; microbial/insulin covariance does not establish adiposity mediation or microbiome-independent weight control.", "confounders_present": [ "Diet was randomized, not microbes; microbial/insulin covariance does not establish adiposity mediation or microbiome-independent weight control." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 31, "pmid": "29489753", "title": "Environment dominates over host genetics in shaping human gut microbiota.", "citation": "Rothschild D, Weissbrod O, Barkan E et al. Environment dominates over host genetics in shaping human gut microbiota. Nature. 2018.", "doi": "10.1038/nature25973", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/29489753/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29489753/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID29489753", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "positive", "what_it_shows": "1046 people show shared-household/diet/drug associations and modest host-genetic contribution to overall community variation; microbes improve phenotype prediction.", "what_it_does_not_show": "Prediction and variance attribution do not establish direction, independence from all host physiology or causal fat accumulation.", "confounders_present": [ "Prediction and variance attribution do not establish direction, independence from all host physiology or causal fat accumulation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 32, "pmid": "23985870", "title": "Richness of human gut microbiome correlates with metabolic markers.", "citation": "Le Chatelier E, Nielsen T, Qin J et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013.", "doi": "10.1038/nature12506", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/23985870/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/23985870/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID23985870", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human observational and longitudinal", "decisive_perturbation": false, "endogenous": false, "direction": "positive", "what_it_shows": "Low microbial gene richness associates with adiposity/metabolic inflammation and later weight gain in a Danish cohort.", "what_it_does_not_show": "Temporal prediction reduces one timing ambiguity but does not randomize diet/host determinants or prove richness itself causal.", "confounders_present": [ "Temporal prediction reduces one timing ambiguity but does not randomize diet/host determinants or prove richness itself causal." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 33, "pmid": "38968121", "title": "Beneficial metabolic effects of PAHSAs depend on the gut microbiota in diet-induced obese mice but not in chow-fed mice.", "citation": "Lee J, Wellenstein K, Rahnavard A et al. Beneficial metabolic effects of PAHSAs depend on the gut microbiota in diet-induced obese mice but not in chow-fed mice. Proceedings of the National Academy of Sciences of the United States of America. 2024.", "doi": "10.1073/pnas.2318691121", "pmcid": "PMC11252816", "url": "https://pubmed.ncbi.nlm.nih.gov/38968121/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38968121/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "UpdateOf: PMID37808673" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID38968121", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse transfer and defined bacterium perturbation", "decisive_perturbation": true, "endogenous": false, "direction": "mixed", "what_it_shows": "PAHSA-treated community transfers insulin sensitivity on high-fat diet; Bt reduces adiposity in female mice, partly dependent on sex hormones.", "what_it_does_not_show": "Effect differs by diet and sex; glucose improvement and female fat reduction must not be combined into universal human mediation; linked preprint is same study.", "confounders_present": [ "Effect differs by diet and sex; glucose improvement and female fat reduction must not be combined into universal human mediation; linked preprint is same study." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 34, "pmid": "38937659", "title": "Ketogenic diet-induced bile acids protect against obesity through reduced calorie absorption.", "citation": "Li X, Yang J, Zhou X et al. Ketogenic diet-induced bile acids protect against obesity through reduced calorie absorption. Nature metabolism. 2024.", "doi": "10.1038/s42255-024-01072-1", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38937659/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38937659/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID38937659", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse strain/enzyme/bile-acid manipulation and human diet study", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "Microbial BSH/strain and bile-acid interventions reduce mouse calorie absorption; human observational and small ketogenic-diet studies show concordant associations.", "what_it_does_not_show": "Human diet intervention is not microbial-mediator randomization; bile-acid replacement does not alone prove the community configuration causes human fat gain.", "confounders_present": [ "Human diet intervention is not microbial-mediator randomization; bile-acid replacement does not alone prove the community configuration causes human fat gain." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 35, "pmid": "30605678", "title": "Parabacteroides distasonis Alleviates Obesity and Metabolic Dysfunctions via Production of Succinate and Secondary Bile Acids.", "citation": "Wang K, Liao M, Zhou N et al. Parabacteroides distasonis Alleviates Obesity and Metabolic Dysfunctions via Production of Succinate and Secondary Bile Acids. Cell reports. 2019.", "doi": "10.1016/j.celrep.2018.12.028", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30605678/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30605678/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID30605678", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "defined mouse strain and metabolite rescue", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "P.distasonis improves ob/ob and high-fat mouse phenotypes; succinate plus secondary bile acids recapitulate metabolic benefits.", "what_it_does_not_show": "Model-specific rescue supports function rather than a universal abundance signature; isolated mediator effects on glucose are distinct from all fat endpoints.", "confounders_present": [ "Model-specific rescue supports function rather than a universal abundance signature; isolated mediator effects on glucose are distinct from all fat endpoints." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 36, "pmid": "39569932", "title": "B. vulgatus ameliorates high-fat diet-induced obesity through modulating intestinal serotonin synthesis and lipid absorption in mice.", "citation": "Wen X, Feng X, Xin F et al. B. vulgatus ameliorates high-fat diet-induced obesity through modulating intestinal serotonin synthesis and lipid absorption in mice. Gut microbes. 2024.", "doi": "10.1080/19490976.2024.2423040", "pmcid": "PMC11583587", "url": "https://pubmed.ncbi.nlm.nih.gov/39569932/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39569932/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID39569932", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse defined bacterium/serotonin pathway perturbation", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "B.vulgatus/cholic acid and epithelial Tph1 contrasts implicate a microbe-metabolite-serotonin axis in lipid absorption and high-fat adiposity.", "what_it_does_not_show": "Host epithelial and dietary dependencies are integral; human colonization and adiposity mediation are not established.", "confounders_present": [ "Host epithelial and dietary dependencies are integral; human colonization and adiposity mediation are not established." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 37, "pmid": "41781619", "title": "Microbiota-mediated induction of beige adipocytes in response to dietary cues.", "citation": "Tanoue T, Nagayama M, Roochana AJA et al. Microbiota-mediated induction of beige adipocytes in response to dietary cues. Nature. 2026.", "doi": "10.1038/s41586-026-10205-3", "pmcid": "PMC13051337", "url": "https://pubmed.ncbi.nlm.nih.gov/41781619/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41781619/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "UpdateOf: PMID39678347" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID41781619", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse defined consortium and pathway rescue", "decisive_perturbation": true, "endogenous": false, "direction": "positive", "what_it_shows": "2026 low-protein diet browning defect in germ-free mice is rescued by defined consortia; bile-acid/FXR and ammonia/FGF21 axes are nonredundant.", "what_it_does_not_show": "Browning genes and dietary compensation are not all clinical fat outcomes; human donor selection is not a human causal trial; linked preprint excluded as duplicate.", "confounders_present": [ "Browning genes and dietary compensation are not all clinical fat outcomes; human donor selection is not a human causal trial; linked preprint excluded as duplicate." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 38, "pmid": "32235930", "title": "Effects of underfeeding and oral vancomycin on gut microbiome and nutrient absorption in humans.", "citation": "Basolo A, Hohenadel M, Ang QY et al. Effects of underfeeding and oral vancomycin on gut microbiome and nutrient absorption in humans. Nature medicine. 2020.", "doi": "10.1038/s41591-020-0801-z", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/32235930/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32235930/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "Absorption-NCT02037295", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "Inpatient crossover feeding plus blinded vancomycin intervention met primary stool-energy-loss endpoints in 25 completers.", "what_it_does_not_show": "Human energy-harvest perturbation is real bounded evidence, but broad antibiotic effects and short timing do not quantify sustained adiposity or a specific microbial mediator.", "confounders_present": [ "Human energy-harvest perturbation is real bounded evidence, but broad antibiotic effects and short timing do not quantify sustained adiposity or a specific microbial mediator." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 39, "pmid": "24336217", "title": "Diet rapidly and reproducibly alters the human gut microbiome.", "citation": "David LA, Maurice CF, Carmody RN et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014.", "doi": "10.1038/nature12820", "pmcid": "PMC3957428", "url": "https://pubmed.ncbi.nlm.nih.gov/24336217/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24336217/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID24336217", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human dietary intervention", "decisive_perturbation": false, "endogenous": false, "direction": "positive", "what_it_shows": "Animal versus plant diets rapidly alter microbial composition and expression, including bile-tolerant and foodborne microbes.", "what_it_does_not_show": "Establishes diet-to-community responsiveness, not community-to-fat causation; transient detection is not durable functional colonization.", "confounders_present": [ "Establishes diet-to-community responsiveness, not community-to-fat causation; transient detection is not durable functional colonization." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 40, "pmid": "30401435", "title": "Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1.", "citation": "Koh A, Molinaro A, Ståhlman M et al. Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1. Cell. 2018.", "doi": "10.1016/j.cell.2018.09.055", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30401435/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30401435/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID30401435", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human association and mouse metabolite perturbation", "decisive_perturbation": true, "endogenous": false, "direction": "positive", "what_it_shows": "Microbial imidazole propionate is enriched in T2D material and impairs mouse glucose/insulin signalling through p38gamma/p62/mTORC1.", "what_it_does_not_show": "Glucose pathology is not adiposity; human metabolite and hepatic pathway associations do not independently establish human fat mediation.", "confounders_present": [ "Glucose pathology is not adiposity; human metabolite and hepatic pathway associations do not independently establish human fat mediation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 41, "pmid": "22863002", "title": "Host remodeling of the gut microbiome and metabolic changes during pregnancy.", "citation": "Koren O, Goodrich JK, Cullender TC et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell. 2012.", "doi": "10.1016/j.cell.2012.07.008", "pmcid": "PMC3505857", "url": "https://pubmed.ncbi.nlm.nih.gov/22863002/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/22863002/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID22863002", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human pregnancy observation and mouse transfer", "decisive_perturbation": true, "endogenous": false, "direction": "positive", "what_it_shows": "Third-trimester community differs from first trimester and transfers more adiposity/insulin insensitivity to germ-free mice.", "what_it_does_not_show": "Normal host pregnancy remodels microbes upstream; adaptive physiology and crude cross-species transfer do not establish common human obesity initiation.", "confounders_present": [ "Normal host pregnancy remodels microbes upstream; adaptive physiology and crude cross-species transfer do not establish common human obesity initiation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 42, "pmid": "18931303", "title": "Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41.", "citation": "Samuel BS, Shaito A, Motoike T et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proceedings of the National Academy of Sciences of the United States of America. 2008.", "doi": "10.1073/pnas.0808567105", "pmcid": "PMC2569967", "url": "https://pubmed.ncbi.nlm.nih.gov/18931303/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/18931303/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID18931303", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse defined two-member community and receptor genetics", "decisive_perturbation": true, "endogenous": false, "direction": "positive", "what_it_shows": "Gpr41loss lowers adiposity in conventional and defined Bt/M.smithii-colonized mice despite similar chow intake, with transit/PYY/energy-harvest links.", "what_it_does_not_show": "Host receptor, community and transit jointly determine effect; no quantified human fat contribution or universal SCFA direction follows.", "confounders_present": [ "Host receptor, community and transit jointly determine effect; no quantified human fat contribution or universal SCFA direction follows." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 43, "pmid": "31147381", "title": "Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time.", "citation": "de Groot P, Scheithauer T, Bakker GJ et al. Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time. Gut. 2020.", "doi": "10.1136/gutjnl-2019-318320", "pmcid": "PMC7034343", "url": "https://pubmed.ncbi.nlm.nih.gov/31147381/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31147381/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "Donor-FMT-NTR4327", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "Donor-characteristic FMT contrast in 22metabolic-syndrome men found worsened clamp sensitivity with metabolic-syndrome donors and bile/immune changes.", "what_it_does_not_show": "Two-week glucose effect is not fat accumulation; no neutral-placebo inference or defined mediator from crude donor material.", "confounders_present": [ "Two-week glucose effect is not fat accumulation; no neutral-placebo inference or defined mediator from crude donor material." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 44, "pmid": "16033867", "title": "Obesity alters gut microbial ecology.", "citation": "Ley RE, Bäckhed F, Turnbaugh P et al. Obesity alters gut microbial ecology. Proceedings of the National Academy of Sciences of the United States of America. 2005.", "doi": "10.1073/pnas.0504978102", "pmcid": "PMC1176910", "url": "https://pubmed.ncbi.nlm.nih.gov/16033867/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/16033867/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID16033867", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "mouse host-genotype microbial profiling", "decisive_perturbation": false, "endogenous": false, "direction": "positive", "what_it_shows": "Ob/ob mice have altered Firmicutes/Bacteroidetes despite shared diet and family comparisons.", "what_it_does_not_show": "Leptin genotype precedes phenotype and microbial ecology; this observational contrast cannot establish microbial direction or phylum-ratio necessity.", "confounders_present": [ "Leptin genotype precedes phenotype and microbial ecology; this observational contrast cannot establish microbial direction or phylum-ratio necessity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 45, "pmid": "17456850", "title": "Metabolic endotoxemia initiates obesity and insulin resistance.", "citation": "Cani PD, Amar J, Iglesias MA et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007.", "doi": "10.2337/db06-1491", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/17456850/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/17456850/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID17456850", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse LPS infusion and CD14 genetics", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "Continuous LPS infusion increases fat/weight and liver insulin resistance; CD14mutants resist many LPS/high-fat phenotypes.", "what_it_does_not_show": "Artificial infusion and host knockout support a defined inflammatory axis, not endogenous human exposure magnitude or all insulin resistance.", "confounders_present": [ "Artificial infusion and host knockout support a defined inflammatory axis, not endogenous human exposure magnitude or all insulin resistance." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 46, "pmid": "23671105", "title": "Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity.", "citation": "Everard A, Belzer C, Geurts L et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proceedings of the National Academy of Sciences of the United States of America. 2013.", "doi": "10.1073/pnas.1219451110", "pmcid": "PMC3670398", "url": "https://pubmed.ncbi.nlm.nih.gov/23671105/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/23671105/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID23671105", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse defined viable-bacterium intervention", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "Live Akkermansia reduces high-fat fat gain and barrier/inflammatory abnormalities; heat-killed preparation was ineffective in this study.", "what_it_does_not_show": "Heat-killing is not equivalent to later pasteurization; formulation/context matter, and human inverse abundance is associative.", "confounders_present": [ "Heat-killing is not equivalent to later pasteurization; formulation/context matter, and human inverse abundance is associative." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 47, "pmid": "18305141", "title": "Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice.", "citation": "Cani PD, Bibiloni R, Knauf C et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008.", "doi": "10.2337/db07-1403", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/18305141/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/18305141/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID18305141", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "mouse antibiotic and CD14 perturbation", "decisive_perturbation": true, "endogenous": false, "direction": "positive", "what_it_shows": "Antibiotics lower endotoxemia, adiposity and inflammation in high-fat/obob mice; CD14deletion partly mimics the phenotype.", "what_it_does_not_show": "Antibiotic pleiotropy and shared investigative programme constrain specificity; no human fat or endogenous LPS mediation estimate.", "confounders_present": [ "Antibiotic pleiotropy and shared investigative programme constrain specificity; no human fat or endogenous LPS mediation estimate." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 48, "pmid": "32108090", "title": "Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice.", "citation": "Kimura I, Miyamoto J, Ohue-Kitano R et al. Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice. Science (New York, N.Y.). 2020.", "doi": "10.1126/science.aaw8429", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/32108090/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32108090/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID32108090", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "maternal mouse microbial/SCFA-receptor developmental manipulation", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "Maternal microbial SCFAs signal through embryonic GPR41/43 and affect later offspring metabolic susceptibility.", "what_it_does_not_show": "Developmental maternal mechanism is distinct from adult recipient obesity and not directly generalized to human fat accumulation.", "confounders_present": [ "Developmental maternal mechanism is distinct from adult recipient obesity and not directly generalized to human fat accumulation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 49, "pmid": "40381616", "title": "Acetylated cellulose suppresses body mass gain through gut commensals consuming host-accessible carbohydrates.", "citation": "Takeuchi T, Miyauchi E, Nakanishi Y et al. Acetylated cellulose suppresses body mass gain through gut commensals consuming host-accessible carbohydrates. Cell metabolism. 2025.", "doi": "10.1016/j.cmet.2025.04.013", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40381616/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40381616/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID40381616", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse prebiotic and commensal perturbation", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "Acetylated cellulose limits body-mass gain through microbiota-dependent host-accessible sugar depletion and altered oxidation.", "what_it_does_not_show": "Mouse prebiotic substrate effect is diet-dependent; bacterial carbohydrate consumption can protect rather than increase host energy harvest.", "confounders_present": [ "Mouse prebiotic substrate effect is diet-dependent; bacterial carbohydrate consumption can protect rather than increase host energy harvest." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 50, "pmid": "35788347", "title": "Population-level Metagenomics Uncovers Distinct Effects of Multiple Medications on the Human Gut Microbiome.", "citation": "Nagata N, Nishijima S, Miyoshi-Akiyama T et al. Population-level Metagenomics Uncovers Distinct Effects of Multiple Medications on the Human Gut Microbiome. Gastroenterology. 2022.", "doi": "10.1053/j.gastro.2022.06.070", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/35788347/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35788347/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID36610810" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID35788347", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human medication metagenomics observational", "decisive_perturbation": false, "endogenous": false, "direction": "positive", "what_it_shows": "4198 people and243repeat samples identify drug/polypharmacy-associated community functions with initiation/cessation tracking.", "what_it_does_not_show": "Confounder evidence is not obesity mechanism; treatment and disease indication share causes, and linked36610810erratum not fully audited.", "confounders_present": [ "Confounder evidence is not obesity mechanism; treatment and disease indication share causes, and linked36610810erratum not fully audited." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 51, "pmid": "28390422", "title": "High-fat feeding rather than obesity drives taxonomical and functional changes in the gut microbiota in mice.", "citation": "Xiao L, Sonne SB, Feng Q et al. High-fat feeding rather than obesity drives taxonomical and functional changes in the gut microbiota in mice. Microbiome. 2017.", "doi": "10.1186/s40168-017-0258-6", "pmcid": "PMC5385073", "url": "https://pubmed.ncbi.nlm.nih.gov/28390422/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28390422/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID28390422", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "mouse diet/genotype/pharmacology contrast", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Diet and mouse strain explain substantial community shifts when high-fat obesity susceptibility is experimentally dissociated.", "what_it_does_not_show": "Community changes need not track fat gain; indomethacin and genotype add effects and do not erase all microbial causality.", "confounders_present": [ "Community changes need not track fat gain; indomethacin and genotype add effects and do not erase all microbial causality." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 52, "pmid": "33975870", "title": "Human and preclinical studies of the host-gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health.", "citation": "Brial F, Chilloux J, Nielsen T et al. Human and preclinical studies of the host-gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health. Gut. 2021.", "doi": "10.1136/gutjnl-2020-323314", "pmcid": "PMC8515120", "url": "https://pubmed.ncbi.nlm.nih.gov/33975870/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33975870/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID33975870", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human association and mouse hippurate infusion", "decisive_perturbation": true, "endogenous": false, "direction": "positive", "what_it_shows": "Urinary hippurate associates with human diet/metabolic state; chronic infusion improves glucose tolerance/insulin secretion in high-fat mice.", "what_it_does_not_show": "Host conjugation contributes to metabolite origin; glucose benefit is not direct human fat reduction or universal microbial mediation.", "confounders_present": [ "Host conjugation contributes to metabolite origin; glucose benefit is not direct human fat reduction or universal microbial mediation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 53, "pmid": "42120725", "title": "Pasteurized Akkermansia muciniphila MucT for weight loss maintenance in people with overweight and obesity: a controlled randomized trial.", "citation": "Mount S, Canfora EE, Jocken JW et al. Pasteurized Akkermansia muciniphila MucT for weight loss maintenance in people with overweight and obesity: a controlled randomized trial. Nature medicine. 2026.", "doi": "10.1038/s41591-026-04394-7", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/42120725/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/42120725/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "Akk-maintenance-NCT05417360", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "2026 pasteurized-Akk RCT 90 people reports primary24 week weight regain1.2vs3.2 kg(P=.012) after successful low-energy-diet loss.", "what_it_does_not_show": "Abstract plus publisher ancillary statements only: fat results, attrition and multiplicity unavailable; nonliving product benefit does not demonstrate living-community causation; company/patent conflicts disclosed.", "confounders_present": [ "Abstract plus publisher ancillary statements only: fat results, attrition and multiplicity unavailable; nonliving product benefit does not demonstrate living-community causation; company/patent conflicts disclosed." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 54, "pmid": "28978426", "title": "Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition.", "citation": "Kootte RS, Levin E, Salojärvi J et al. Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition. Cell metabolism. 2017.", "doi": "10.1016/j.cmet.2017.09.008", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/28978426/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28978426/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID28978426", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "Lean-donor FMT improves six-week insulin sensitivity in selected baseline communities, with no metabolic effect at18 weeks.", "what_it_does_not_show": "Metabolic responder stratification is not prevalidated adiposity selection; transient clamp effect is not sustained fat control.", "confounders_present": [ "Metabolic responder stratification is not prevalidated adiposity selection; transient clamp effect is not sustained fat control." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 55, "pmid": "32150549", "title": "Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial.", "citation": "Yu EW, Gao L, Stastka P et al. Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial. PLoS medicine. 2020.", "doi": "10.1371/journal.pmed.1003051", "pmcid": "PMC7062239", "url": "https://pubmed.ncbi.nlm.nih.gov/32150549/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32150549/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "FMT-TRIM-NCT02530385", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph1, 1:Methods:paragraph3, 1:Methods:paragraph6, 1:Methods:paragraph7, 2:Results:paragraph0, 2:Results:paragraph6, 2:Results:paragraph13, 2:Results:paragraph14, 2:Results:paragraph15, 2:Results:paragraph16, 2:Results:paragraph17. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "negative", "what_it_shows": "FMT-TRIM randomized 24; primary clamp null and secondary weight/fat mass null despite variable donor engraftment.", "what_it_does_not_show": "Original Methods power only for large clamp effects; pilot null is not equivalence, donor strength differs and16SASVs cannot uniquely resolve all strains.", "confounders_present": [ "Original Methods power only for large clamp effects; pilot null is not equivalence, donor strength differs and16SASVs cannot uniquely resolve all strains." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 56, "pmid": "34226737", "title": "Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial.", "citation": "Mocanu V, Zhang Z, Deehan EC et al. Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial. Nature medicine. 2021.", "doi": "10.1038/s41591-021-01399-2", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/34226737/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34226737/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "Mocanu-NCT03477916", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "70-person FMT/fiber factorial reports six-week HOMA improvement in FMT-low-fermentable arm.", "what_it_does_not_show": "Abstract chiefly reports within-armP=.02: significance versus other null arms is not a between-arm treatment effect; original contrasts and adiposity mediation unverified.", "confounders_present": [ "Abstract chiefly reports within-armP=.02: significance versus other null arms is not a between-arm treatment effect; original contrasts and adiposity mediation unverified." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 57, "pmid": "38685731", "title": "Recipient microbiome-related features predicting metabolic improvement following fecal microbiota transplantation in adults with severe obesity and metabolic syndrome: a secondary analysis of a phase 2 clinical trial.", "citation": "Zhang Z, Mocanu V, Deehan EC et al. Recipient microbiome-related features predicting metabolic improvement following fecal microbiota transplantation in adults with severe obesity and metabolic syndrome: a secondary analysis of a phase 2 clinical trial. Gut microbes. 2024.", "doi": "10.1080/19490976.2024.2345134", "pmcid": "PMC11062372", "url": "https://pubmed.ncbi.nlm.nih.gov/38685731/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38685731/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "Mocanu-NCT03477916", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Weak", "system": "human trial secondary analysis", "decisive_perturbation": false, "endogenous": false, "direction": "positive", "what_it_shows": "Mocanu trial follow-up groups21responders8nonresponders; baseline taxa/engraftment correlate with HOMA response.", "what_it_does_not_show": "Same family and response-defined subgroups; predictionAUC.70 is not external validation or new randomized human fat causation.", "confounders_present": [ "Same family and response-defined subgroups; predictionAUC.70 is not external validation or new randomized human fat causation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 58, "pmid": "27411009", "title": "Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: A Randomized Double-Blind Placebo-Controlled Trial.", "citation": "Reijnders D, Goossens GH, Hermes GD et al. Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: A Randomized Double-Blind Placebo-Controlled Trial. Cell metabolism. 2016.", "doi": "10.1016/j.cmet.2016.06.016", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/27411009/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/27411009/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID27411009", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "negative", "what_it_shows": "57-obese-prediabetic-men antibiotic RCT changes communities/SCFA/bile but not clinically relevant energy harvest, insulin sensitivity or adipocyte size through8 weeks.", "what_it_does_not_show": "Short broad intervention cannot falsify all configurations; null adipocyte size is not all total-fat endpoints, and correction completeness is limited.", "confounders_present": [ "Short broad intervention cannot falsify all configurations; null adipocyte size is not all total-fat endpoints, and correction completeness is limited." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 59, "pmid": "21543530", "title": "Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans.", "citation": "Jumpertz R, Le DS, Turnbaugh PJ et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. The American journal of clinical nutrition. 2011.", "doi": "10.3945/ajcn.110.010132", "pmcid": "PMC3127503", "url": "https://pubmed.ncbi.nlm.nih.gov/21543530/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/21543530/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID21543530", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human controlled feeding and microbiome association", "decisive_perturbation": false, "endogenous": false, "direction": "positive", "what_it_shows": "Inpatient energy-balance study in 12lean9 obese links nutrient load, stool energy and Firmicutes/Bacteroidetes, including an approximately150 kcal association.", "what_it_does_not_show": "Dietary load changes microbes and absorption together; microbial proportions were not randomized and150 kcal is not a demonstrated sustained fat-gain cause.", "confounders_present": [ "Dietary load changes microbes and absorption together; microbial proportions were not randomized and150 kcal is not a demonstrated sustained fat-gain cause." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 60, "pmid": "20441670", "title": "Absence of intestinal microbiota does not protect mice from diet-induced obesity.", "citation": "Fleissner CK, Huebel N, Abd El-Bary MM et al. Absence of intestinal microbiota does not protect mice from diet-induced obesity. The British journal of nutrition. 2010.", "doi": "10.1017/S0007114510001303", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/20441670/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/20441670/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID20441670", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "germ-free/conventional mouse diet contrast", "decisive_perturbation": false, "endogenous": false, "direction": "negative", "what_it_shows": "Germ-free C3Hmice gain more fat on one high-fat formula while Western diet behaves differently; Fiaf differences do not match universal protection.", "what_it_does_not_show": "Diet/strain boundary challenges necessity and simple Fiaf universalization; does not negate positive mechanisms in other hosts or substrates.", "confounders_present": [ "Diet/strain boundary challenges necessity and simple Fiaf universalization; does not negate positive mechanisms in other hosts or substrates." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 61, "pmid": "25500202", "title": "Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults.", "citation": "Chambers ES, Viardot A, Psichas A et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut. 2015.", "doi": "10.1136/gutjnl-2014-307913", "pmcid": "PMC4680171", "url": "https://pubmed.ncbi.nlm.nih.gov/25500202/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25500202/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "Propionate-NCT00750438", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Methods:paragraph3, 1:Methods:paragraph4, 1:Methods:paragraph5, 1:Methods:paragraph7, 1:Methods:paragraph9, 2:Results:paragraph1, 2:Results:paragraph5, 2:Results:paragraph6, 2:Results:paragraph9, 2:Results:paragraph10, 2:Results:paragraph13. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "Propionate ester reduces threshold-defined weight-gain events and secondary intra-abdominal-fat distribution; acute appetite/hormone perturbation works.", "what_it_does_not_show": "Original24 week mean weight differenceP=.099 and total-adipose difference null;49/60 completers and32composition data; ester delivery is not randomized living community.", "confounders_present": [ "Original24 week mean weight differenceP=.099 and total-adipose difference null;49/60 completers and32composition data; ester delivery is not randomized living community." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 62, "pmid": "39391015", "title": "Increase in colonic PRopionate as a method of prEVENTing weight gain over 12 months in adults aged 20-40 years (iPREVENT): a multi-centre, double-blind, randomised, parallel-group trial.", "citation": "Pugh JE, Petropoulou K, Vasconcelos JC et al. Increase in colonic PRopionate as a method of prEVENTing weight gain over 12 months in adults aged 20-40 years (iPREVENT): a multi-centre, double-blind, randomised, parallel-group trial. EClinicalMedicine. 2024.", "doi": "10.1016/j.eclinm.2024.102844", "pmcid": "PMC11466568", "url": "https://pubmed.ncbi.nlm.nih.gov/39391015/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39391015/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "iPREVENT-ISRCTN16299902", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph1, 1:Methods:paragraph3, 1:Methods:paragraph4, 1:Methods:paragraph6, 1:Methods:paragraph8, 1:Methods:paragraph11, 1:Methods:paragraph12, 1:Methods:paragraph13, 1:Methods:paragraph22, 1:Methods:paragraph23, 1:Methods:paragraph28, 1:Methods:paragraph29, 1:Methods:paragraph30, 2:Results:paragraph0, 2:Results:paragraph4, 2:Results:paragraph5, 2:Results:paragraph10, 2:Results:paragraph14, 2:Results:paragraph15, 2:Results:paragraph16, 2:Results:paragraph18. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "negative", "what_it_shows": "iPREVENT270 randomized:12 month primary weight difference1.02kgCI-.37to2.41 null; secondary fat-mass difference.07kgCI-1.07to1.21 null.", "what_it_does_not_show": "Original model used256 with any follow-up,226at12 months; adherence and low control weight gain constrain exposure/generalization, not permission to declare overall efficacy.", "confounders_present": [ "Original model used256 with any follow-up,226at12 months; adherence and low control weight gain constrain exposure/generalization, not permission to declare overall efficacy." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 63, "pmid": "24316517", "title": "Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity.", "citation": "Vrieze A, Out C, Fuentes S et al. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. Journal of hepatology. 2014.", "doi": "10.1016/j.jhep.2013.11.034", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/24316517/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24316517/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "Antibiotic-NTR2566", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "Seven-day vancomycin versus amoxicillin changes microbes/bile acids and worsens peripheral clamp sensitivity in 20 men.", "what_it_does_not_show": "Active-antibiotic comparator and short treatment do not isolate a microbial mediator or establish fat gain.", "confounders_present": [ "Active-antibiotic comparator and short treatment do not isolate a microbial mediator or establish fat gain." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 64, "pmid": "17210919", "title": "Mechanisms underlying the resistance to diet-induced obesity in germ-free mice.", "citation": "Bäckhed F, Manchester JK, Semenkovich CF et al. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proceedings of the National Academy of Sciences of the United States of America. 2007.", "doi": "10.1073/pnas.0605374104", "pmcid": "PMC1764762", "url": "https://pubmed.ncbi.nlm.nih.gov/17210919/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/17210919/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID17210919", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse germ-free and Fiaf genetics", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "Germ-free Western-diet protection is lost with Fiafdeletion; AMPK/fatty-acid oxidation supports complementary host mechanisms.", "what_it_does_not_show": "Diet/strain counterstudy limits universal Fiaf or microbiota necessity; protection is not endogenous human causal weight evidence.", "confounders_present": [ "Diet/strain counterstudy limits universal Fiaf or microbiota necessity; protection is not endogenous human causal weight evidence." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 65, "pmid": "32860791", "title": "Effects of Diet-Modulated Autologous Fecal Microbiota Transplantation on Weight Regain.", "citation": "Rinott E, Youngster I, Yaskolka Meir A et al. Effects of Diet-Modulated Autologous Fecal Microbiota Transplantation on Weight Regain. Gastroenterology. 2021.", "doi": "10.1053/j.gastro.2020.08.041", "pmcid": "PMC7755729", "url": "https://pubmed.ncbi.nlm.nih.gov/32860791/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32860791/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "DIRECT-PLUS-NCT03020186", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: PMC original author manuscript: Methods/Statistical analysis and Results/Weight regain, lines300-305,335-342,396-413. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional and mouse validation", "decisive_perturbation": true, "endogenous": false, "direction": "mixed", "what_it_shows": "Rinott aFMT had overall primary regain null(P=.28), but green-Mediterranean interaction(P=.03) and diet-specific benefit(P=.02); Methods confirmITT90 with one imputation.", "what_it_does_not_show": "Diet-specific weight result is not uniform FMT or total-fat success; original protocol/supplement pre-specification not independently audited; crude transfer remains nonspecific.", "confounders_present": [ "Diet-specific weight result is not uniform FMT or total-fat success; original protocol/supplement pre-specification not independently audited; crude transfer remains nonspecific." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 66, "pmid": "37796016", "title": "Successful weight regain attenuation by autologous fecal microbiota transplantation is associated with non-core gut microbiota changes during weight loss; randomized controlled trial.", "citation": "Kamer O, Rinott E, Tsaban G et al. Successful weight regain attenuation by autologous fecal microbiota transplantation is associated with non-core gut microbiota changes during weight loss; randomized controlled trial. Gut microbes. 2023.", "doi": "10.1080/19490976.2023.2264457", "pmcid": "PMC10557561", "url": "https://pubmed.ncbi.nlm.nih.gov/37796016/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37796016/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "DIRECT-PLUS-NCT03020186", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human trial secondary analysis", "decisive_perturbation": false, "endogenous": false, "direction": "positive", "what_it_shows": "DIRECT-PLUS secondary analysis associates low-core/high-noncore community change with aFMT weight maintenance.", "what_it_does_not_show": "Same trial family, response-related multivariate subgroup and taxa selection; not independent efficacy replication or prospective validation.", "confounders_present": [ "Same trial family, response-related multivariate subgroup and taxa selection; not independent efficacy replication or prospective validation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 67, "pmid": "23652017", "title": "The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43.", "citation": "Kimura I, Ozawa K, Inoue D et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nature communications. 2013.", "doi": "10.1038/ncomms2852", "pmcid": "PMC3674247", "url": "https://pubmed.ncbi.nlm.nih.gov/23652017/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/23652017/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID23652017", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 0:Results:paragraph0, 0:Results:paragraph1, 0:Results:paragraph2, 0:Results:paragraph3, 0:Results:paragraph4, 0:Results:paragraph5, 0:Results:paragraph6, 0:Results:paragraph7, 0:Results:paragraph8, 1:Discussion:paragraph4, 1:Discussion:paragraph5, 1:Discussion:paragraph6, 2:Methods:paragraph0, 2:Methods:paragraph1, 9:Main text (unsectioned body paragraphs):paragraph2, 9:Main text (unsectioned body paragraphs):paragraph3. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse receptor genetics and microbial/acetate rescue", "decisive_perturbation": true, "endogenous": true, "direction": "positive", "what_it_shows": "GPR43loss/OE effects disappear with germ-free/antibiotic conditions; conventionalization and acetate rescue restore receptor-dependent fat effects.", "what_it_does_not_show": "Original strains differ between KO and OE backgrounds; lifelong manipulation and receptor/tissue specificity limit universal SCFA or human obesity inference.", "confounders_present": [ "Original strains differ between KO and OE backgrounds; lifelong manipulation and receptor/tissue specificity limit universal SCFA or human obesity inference." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } }, { "n": 68, "pmid": "26638070", "title": "Gut Microbiota Orchestrates Energy Homeostasis during Cold.", "citation": "Chevalier C, Stojanović O, Colin DJ et al. Gut Microbiota Orchestrates Energy Homeostasis during Cold. Cell. 2015.", "doi": "10.1016/j.cell.2015.11.004", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/26638070/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26638070/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID26638070", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse cold-community transfer and strain amendment", "decisive_perturbation": true, "endogenous": false, "direction": "mixed", "what_it_shows": "Cold-community transfer drives browning/fat loss followed by absorptive compensation; Akk co-transfer diminishes intestinal adaptation.", "what_it_does_not_show": "Physiological demand, substrate and compensation change the sign/magnitude; a protective transfer is not a universal human fat-producing configuration.", "confounders_present": [ "Physiological demand, substrate and compensation change the sign/magnitude; a protective transfer is not a universal human fat-producing configuration." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] } } ], "verification_summary": { "load_bearing_claims_checked": 72, "verified": 72, "unverified": 0, "contradicted": 0, "note": "Verified attribution is distinct from mechanism truth or complete body access." }, "factual_issues_found": [], "cap_rules_applied": [], "cap_precedence_resolutions": [ { "collision": "Perturbation in a defined setting versus broader inference", "subclaim_scope_cap_binds_on": "Gut microbial configuration causally drives human fat accumulation through energy harvest, microbial products and endocrine signalling, beyond diet and host physiology.", "subclaim_scope_threshold_binds_on": "The precise experimentally tested subclaim scope", "resolution": "Rubric04 transfer and rescue thresholds bind the recipient-animal scope. Universal forced-transfer cap5 binds the inference from that experiment to endogenous humans, not a randomized human fat contrast. Defined mouse strains, host pathways and rescue converge on SC1Ζ; independently controlled human adiposity interventions support SC2Δ. They do not demonstrate the same molecule or community function in all humans, so Ε generalization is not met. A metabolically positive trial is not treated as a fat trial. No weakest-leg cap is reapplied to the whole case.", "note": "Convergent lines are assessed as a set; one weak leg is not re-capped over the assembled case." } ], "boundary_check_BGD": [ { "subclaim_id": "SC1", "field_valid_perturbation_quote": "\n- Gnotobiotic or transfer experiment showing phenotype movement, at minimum\n- Even without defined-consortium precision or robust rescue, a transfer paradigm in vivo is the minimum that crosses this threshold\n\nPer **Cap precedence** above, a gnotobiotic or forced-transfer experiment crosses Δ for the recipient-animal subclaim it was actually run in, while universal cap 5 (seeding or forced-transfer paradigms cap at Γ) still blocks the inference from that result to endogenous human biology — score the two scopes separately rather than choosing between the rules.", "qualifying_evidence_present": "yes", "qualifying_evidence_citation": "PMID17183312, PMID24009397, PMID25417156, PMID28860383, PMID15505215, PMID25731162, PMID31604271, PMID41197631, PMID29649441, PMID26740296, PMID27892954, PMID38996548, PMID38968121, PMID38937659, PMID30605678, PMID39569932, PMID41781619, PMID30401435, PMID22863002, PMID18931303, PMID17456850, PMID23671105, PMID18305141, PMID32108090, PMID40381616, PMID33975870, PMID17210919, PMID23652017, PMID26638070", "gamma_hard_rules_triggered": [], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "yes", "perturbation_result_note": "Transfer, cultured-community/strain amendment and rescue repeatedly move recipient adiposity, with defined functions and host-receptor tests addressing distinct errors [1-4,6-7,10,12-15,17,28,33-37,41-42,45-49,64,67-68]. The broad defined-recipient claim reaches Ζ across distinct mechanisms; this does not promote every individual strain or infer human causality.", "ceiling_from_boundary_check": "Δ or higher" }, { "subclaim_id": "SC2", "field_valid_perturbation_quote": "\n- Gnotobiotic or transfer experiment showing phenotype movement, at minimum\n- Even without defined-consortium precision or robust rescue, a transfer paradigm in vivo is the minimum that crosses this threshold\n\nPer **Cap precedence** above, a gnotobiotic or forced-transfer experiment crosses Δ for the recipient-animal subclaim it was actually run in, while universal cap 5 (seeding or forced-transfer paradigms cap at Γ) still blocks the inference from that result to endogenous human biology — score the two scopes separately rather than choosing between the rules.", "qualifying_evidence_present": "yes", "qualifying_evidence_citation": "PMID25417156, PMID33346848, PMID22728514, PMID41197631, PMID31263284, PMID27892954, PMID33785557, PMID30262813, PMID39456659, PMID24299712, PMID40877311, PMID26466123, PMID38996548, PMID38937659, PMID32235930, PMID22863002, PMID31147381, PMID42120725, PMID28978426, PMID34226737, PMID25500202, PMID24316517, PMID32860791, PMID26638070", "gamma_hard_rules_triggered": [], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "yes", "perturbation_result_note": "The Δ crossing rests on a randomized human perturbation with a positive registered primary endpoint in the scoped population: the 2026 pasteurized-Akkermansia weight-maintenance trial [53]. Obese-population strain/formulation trial signals and the randomized FMT fat-distribution contrast add supporting human evidence [9,21,23-25], but GutBugs was null on its BMI-SDS primary and on total body-fat percentage, so its prespecified secondary android/gynoid result, obtained without multiplicity control, supports rather than supplies the crossing. VSL3 high-energy-diet fat-gain attenuation [26] supports human physiology but is outside the registered obese-recipient gate. The 2026 pasteurized-Akk primary weight-maintenance benefit is additional clinical evidence [53], but does not alone establish a living-community or total-fat mechanism. Primary nulls, selected analyses, incomplete mediator attribution and access prevent Ε generalization [5,16,20,22,54-62,65-66]. No universal necessity or primacy burden is imposed on this contributory subclaim.", "ceiling_from_boundary_check": "Δ or higher" }, { "subclaim_id": "SC3", "field_valid_perturbation_quote": "\n- Gnotobiotic or transfer experiment showing phenotype movement, at minimum\n- Even without defined-consortium precision or robust rescue, a transfer paradigm in vivo is the minimum that crosses this threshold\n\nPer **Cap precedence** above, a gnotobiotic or forced-transfer experiment crosses Δ for the recipient-animal subclaim it was actually run in, while universal cap 5 (seeding or forced-transfer paradigms cap at Γ) still blocks the inference from that result to endogenous human biology — score the two scopes separately rather than choosing between the rules.", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "PMID33346848, PMID22728514, PMID31263284, PMID33785557, PMID39456659, PMID40877311, PMID26466123, PMID38968121, PMID32235930, PMID30401435, PMID31147381, PMID33975870, PMID28978426, PMID34226737, PMID25500202, PMID24316517", "gamma_hard_rules_triggered": [ "The claimed inference from metabolic biomarkers to body-fat control is not established without the adiposity outcome and causal link." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Glucose/insulin and inflammatory effects do not by themselves establish body-fat control. Mouse depletion, human engraftment and clamp interventions can change those readouts without corresponding fat changes [11,14,18-19,38,40,43,52,54-59,63]. Positive fat trials retain their own credit in SC2; metabolic efficacy is not dismissed because complete mediation is absent.", "ceiling_from_boundary_check": "Γ" } ], "thresholds_tested": [ { "subclaim_id": "SC1", "threshold": "Δ", "requirement_quoted": "Requires a transfer paradigm or causal perturbation in vivo.", "satisfied": "yes", "supporting_evidence": [ "[1] Obese-donor community transfers greater fat accumulation and energy-harvest capacity to germ-free recipients.", "[2] Discordant-twin fecal communities and cultured collections transfer adiposity; lean-community invasion rescues in a diet-dependent manner.", "[3] Human heritable Christensenellaceae associate with low BMI; cultured C.minuta amendment reduces recipient mouse weight gain.", "[4] Microbial control of circadian NFIL3 links innate immune signalling to intestinal lipid absorption and body composition.", "[6] Conventionalization increases body fat despite lower intake; Fiaf knockout experiments implicate host lipid-storage regulation.", "[7] Emulsifier-associated communities transfer inflammation/metabolic phenotype; germ-free contrasts support a microbial contribution.", "[10] Epithelial HDAC3 integrates microbial/circadian cues, induces Cd36/lipid uptake and promotes diet-induced obesity.", "[12] Turicibacter and purified bacterial lipids suppress host ceramides/fat uptake and obesity; dietary fat reduces colonization and continuous dosing restores benefit.", "[13] Jejunal microbiota from high-fat donors increases recipient lipid absorption even on low-fat diet; conditioned media induce epithelial uptake genes.", "[15] FXR genotype and germ-free/conventional contrasts change diet-induced adiposity; donor community transfers phenotype.", "[17] Pasteurization and Amuc1100/TLR2-linked protein partly recapitulate metabolic/fat benefits in mice; preliminary human safety was reported.", "[28] 631obese374control cohort associates Megamonas with obesity; M.rupellensis and heterologous iolG expression promote mouse lipid absorption, with myo-inositol functional support.", "[33] PAHSA-treated community transfers insulin sensitivity on high-fat diet; Bt reduces adiposity in female mice, partly dependent on sex hormones.", "[34] Microbial BSH/strain and bile-acid interventions reduce mouse calorie absorption; human observational and small ketogenic-diet studies show concordant associations.", "[35] P.distasonis improves ob/ob and high-fat mouse phenotypes; succinate plus secondary bile acids recapitulate metabolic benefits.", "[36] B.vulgatus/cholic acid and epithelial Tph1 contrasts implicate a microbe-metabolite-serotonin axis in lipid absorption and high-fat adiposity.", "[37] 2026 low-protein diet browning defect in germ-free mice is rescued by defined consortia; bile-acid/FXR and ammonia/FGF21 axes are nonredundant.", "[40] Microbial imidazole propionate is enriched in T2D material and impairs mouse glucose/insulin signalling through p38gamma/p62/mTORC1.", "[41] Third-trimester community differs from first trimester and transfers more adiposity/insulin insensitivity to germ-free mice.", "[42] Gpr41loss lowers adiposity in conventional and defined Bt/M.smithii-colonized mice despite similar chow intake, with transit/PYY/energy-harvest links.", "[45] Continuous LPS infusion increases fat/weight and liver insulin resistance; CD14mutants resist many LPS/high-fat phenotypes.", "[46] Live Akkermansia reduces high-fat fat gain and barrier/inflammatory abnormalities; heat-killed preparation was ineffective in this study.", "[47] Antibiotics lower endotoxemia, adiposity and inflammation in high-fat/obob mice; CD14deletion partly mimics the phenotype.", "[48] Maternal microbial SCFAs signal through embryonic GPR41/43 and affect later offspring metabolic susceptibility.", "[49] Acetylated cellulose limits body-mass gain through microbiota-dependent host-accessible sugar depletion and altered oxidation.", "[52] Urinary hippurate associates with human diet/metabolic state; chronic infusion improves glucose tolerance/insulin secretion in high-fat mice.", "[64] Germ-free Western-diet protection is lost with Fiafdeletion; AMPK/fatty-acid oxidation supports complementary host mechanisms.", "[67] GPR43loss/OE effects disappear with germ-free/antibiotic conditions; conventionalization and acetate rescue restore receptor-dependent fat effects.", "[68] Cold-community transfer drives browning/fat loss followed by absorptive compensation; Akk co-transfer diminishes intestinal adaptation." ], "what_would_cross_it": "" }, { "subclaim_id": "SC1", "threshold": "Ε", "requirement_quoted": "Requires context-specific causal effect with defined limits. A transferable phenotype exists, but microbial identity or generalizability remains incomplete.", "satisfied": "yes", "supporting_evidence": [ "[1] Obese-donor community transfers greater fat accumulation and energy-harvest capacity to germ-free recipients.", "[2] Discordant-twin fecal communities and cultured collections transfer adiposity; lean-community invasion rescues in a diet-dependent manner.", "[3] Human heritable Christensenellaceae associate with low BMI; cultured C.minuta amendment reduces recipient mouse weight gain.", "[4] Microbial control of circadian NFIL3 links innate immune signalling to intestinal lipid absorption and body composition.", "[6] Conventionalization increases body fat despite lower intake; Fiaf knockout experiments implicate host lipid-storage regulation.", "[7] Emulsifier-associated communities transfer inflammation/metabolic phenotype; germ-free contrasts support a microbial contribution.", "[10] Epithelial HDAC3 integrates microbial/circadian cues, induces Cd36/lipid uptake and promotes diet-induced obesity.", "[12] Turicibacter and purified bacterial lipids suppress host ceramides/fat uptake and obesity; dietary fat reduces colonization and continuous dosing restores benefit.", "[13] Jejunal microbiota from high-fat donors increases recipient lipid absorption even on low-fat diet; conditioned media induce epithelial uptake genes.", "[15] FXR genotype and germ-free/conventional contrasts change diet-induced adiposity; donor community transfers phenotype.", "[17] Pasteurization and Amuc1100/TLR2-linked protein partly recapitulate metabolic/fat benefits in mice; preliminary human safety was reported.", "[28] 631obese374control cohort associates Megamonas with obesity; M.rupellensis and heterologous iolG expression promote mouse lipid absorption, with myo-inositol functional support.", "[33] PAHSA-treated community transfers insulin sensitivity on high-fat diet; Bt reduces adiposity in female mice, partly dependent on sex hormones.", "[34] Microbial BSH/strain and bile-acid interventions reduce mouse calorie absorption; human observational and small ketogenic-diet studies show concordant associations.", "[35] P.distasonis improves ob/ob and high-fat mouse phenotypes; succinate plus secondary bile acids recapitulate metabolic benefits.", "[36] B.vulgatus/cholic acid and epithelial Tph1 contrasts implicate a microbe-metabolite-serotonin axis in lipid absorption and high-fat adiposity.", "[37] 2026 low-protein diet browning defect in germ-free mice is rescued by defined consortia; bile-acid/FXR and ammonia/FGF21 axes are nonredundant.", "[40] Microbial imidazole propionate is enriched in T2D material and impairs mouse glucose/insulin signalling through p38gamma/p62/mTORC1.", "[41] Third-trimester community differs from first trimester and transfers more adiposity/insulin insensitivity to germ-free mice.", "[42] Gpr41loss lowers adiposity in conventional and defined Bt/M.smithii-colonized mice despite similar chow intake, with transit/PYY/energy-harvest links.", "[45] Continuous LPS infusion increases fat/weight and liver insulin resistance; CD14mutants resist many LPS/high-fat phenotypes.", "[46] Live Akkermansia reduces high-fat fat gain and barrier/inflammatory abnormalities; heat-killed preparation was ineffective in this study.", "[47] Antibiotics lower endotoxemia, adiposity and inflammation in high-fat/obob mice; CD14deletion partly mimics the phenotype.", "[48] Maternal microbial SCFAs signal through embryonic GPR41/43 and affect later offspring metabolic susceptibility.", "[49] Acetylated cellulose limits body-mass gain through microbiota-dependent host-accessible sugar depletion and altered oxidation.", "[52] Urinary hippurate associates with human diet/metabolic state; chronic infusion improves glucose tolerance/insulin secretion in high-fat mice.", "[64] Germ-free Western-diet protection is lost with Fiafdeletion; AMPK/fatty-acid oxidation supports complementary host mechanisms.", "[67] GPR43loss/OE effects disappear with germ-free/antibiotic conditions; conventionalization and acetate rescue restore receptor-dependent fat effects.", "[68] Cold-community transfer drives browning/fat loss followed by absorptive compensation; Akk co-transfer diminishes intestinal adaptation." ], "what_would_cross_it": "" }, { "subclaim_id": "SC1", "threshold": "Ζ", "requirement_quoted": "Requires:\n- Defined consortium or strain-level causal evidence\n- Rescue logic\n- Replication across at least two relevant models or cohorts", "satisfied": "yes", "supporting_evidence": [ "[1] Obese-donor community transfers greater fat accumulation and energy-harvest capacity to germ-free recipients.", "[2] Discordant-twin fecal communities and cultured collections transfer adiposity; lean-community invasion rescues in a diet-dependent manner.", "[3] Human heritable Christensenellaceae associate with low BMI; cultured C.minuta amendment reduces recipient mouse weight gain.", "[4] Microbial control of circadian NFIL3 links innate immune signalling to intestinal lipid absorption and body composition.", "[6] Conventionalization increases body fat despite lower intake; Fiaf knockout experiments implicate host lipid-storage regulation.", "[7] Emulsifier-associated communities transfer inflammation/metabolic phenotype; germ-free contrasts support a microbial contribution.", "[10] Epithelial HDAC3 integrates microbial/circadian cues, induces Cd36/lipid uptake and promotes diet-induced obesity.", "[12] Turicibacter and purified bacterial lipids suppress host ceramides/fat uptake and obesity; dietary fat reduces colonization and continuous dosing restores benefit.", "[13] Jejunal microbiota from high-fat donors increases recipient lipid absorption even on low-fat diet; conditioned media induce epithelial uptake genes.", "[15] FXR genotype and germ-free/conventional contrasts change diet-induced adiposity; donor community transfers phenotype.", "[17] Pasteurization and Amuc1100/TLR2-linked protein partly recapitulate metabolic/fat benefits in mice; preliminary human safety was reported.", "[28] 631obese374control cohort associates Megamonas with obesity; M.rupellensis and heterologous iolG expression promote mouse lipid absorption, with myo-inositol functional support.", "[33] PAHSA-treated community transfers insulin sensitivity on high-fat diet; Bt reduces adiposity in female mice, partly dependent on sex hormones.", "[34] Microbial BSH/strain and bile-acid interventions reduce mouse calorie absorption; human observational and small ketogenic-diet studies show concordant associations.", "[35] P.distasonis improves ob/ob and high-fat mouse phenotypes; succinate plus secondary bile acids recapitulate metabolic benefits.", "[36] B.vulgatus/cholic acid and epithelial Tph1 contrasts implicate a microbe-metabolite-serotonin axis in lipid absorption and high-fat adiposity.", "[37] 2026 low-protein diet browning defect in germ-free mice is rescued by defined consortia; bile-acid/FXR and ammonia/FGF21 axes are nonredundant.", "[40] Microbial imidazole propionate is enriched in T2D material and impairs mouse glucose/insulin signalling through p38gamma/p62/mTORC1.", "[41] Third-trimester community differs from first trimester and transfers more adiposity/insulin insensitivity to germ-free mice.", "[42] Gpr41loss lowers adiposity in conventional and defined Bt/M.smithii-colonized mice despite similar chow intake, with transit/PYY/energy-harvest links.", "[45] Continuous LPS infusion increases fat/weight and liver insulin resistance; CD14mutants resist many LPS/high-fat phenotypes.", "[46] Live Akkermansia reduces high-fat fat gain and barrier/inflammatory abnormalities; heat-killed preparation was ineffective in this study.", "[47] Antibiotics lower endotoxemia, adiposity and inflammation in high-fat/obob mice; CD14deletion partly mimics the phenotype.", "[48] Maternal microbial SCFAs signal through embryonic GPR41/43 and affect later offspring metabolic susceptibility.", "[49] Acetylated cellulose limits body-mass gain through microbiota-dependent host-accessible sugar depletion and altered oxidation.", "[52] Urinary hippurate associates with human diet/metabolic state; chronic infusion improves glucose tolerance/insulin secretion in high-fat mice.", "[64] Germ-free Western-diet protection is lost with Fiafdeletion; AMPK/fatty-acid oxidation supports complementary host mechanisms.", "[67] GPR43loss/OE effects disappear with germ-free/antibiotic conditions; conventionalization and acetate rescue restore receptor-dependent fat effects.", "[68] Cold-community transfer drives browning/fat loss followed by absorptive compensation; Akk co-transfer diminishes intestinal adaptation." ], "what_would_cross_it": "" }, { "subclaim_id": "SC1", "threshold": "Η", "requirement_quoted": "Requires:\n- Defined consortium or factor rescue in multiple contexts\n- Narrowed mechanism\n- Strong exclusion of diet, housing, batch, and handling confounds", "satisfied": "no", "supporting_evidence": [ "[1] Obese-donor community transfers greater fat accumulation and energy-harvest capacity to germ-free recipients.", "[2] Discordant-twin fecal communities and cultured collections transfer adiposity; lean-community invasion rescues in a diet-dependent manner.", "[3] Human heritable Christensenellaceae associate with low BMI; cultured C.minuta amendment reduces recipient mouse weight gain.", "[4] Microbial control of circadian NFIL3 links innate immune signalling to intestinal lipid absorption and body composition.", "[6] Conventionalization increases body fat despite lower intake; Fiaf knockout experiments implicate host lipid-storage regulation.", "[7] Emulsifier-associated communities transfer inflammation/metabolic phenotype; germ-free contrasts support a microbial contribution.", "[10] Epithelial HDAC3 integrates microbial/circadian cues, induces Cd36/lipid uptake and promotes diet-induced obesity.", "[12] Turicibacter and purified bacterial lipids suppress host ceramides/fat uptake and obesity; dietary fat reduces colonization and continuous dosing restores benefit.", "[13] Jejunal microbiota from high-fat donors increases recipient lipid absorption even on low-fat diet; conditioned media induce epithelial uptake genes.", "[15] FXR genotype and germ-free/conventional contrasts change diet-induced adiposity; donor community transfers phenotype.", "[17] Pasteurization and Amuc1100/TLR2-linked protein partly recapitulate metabolic/fat benefits in mice; preliminary human safety was reported.", "[28] 631obese374control cohort associates Megamonas with obesity; M.rupellensis and heterologous iolG expression promote mouse lipid absorption, with myo-inositol functional support.", "[33] PAHSA-treated community transfers insulin sensitivity on high-fat diet; Bt reduces adiposity in female mice, partly dependent on sex hormones.", "[34] Microbial BSH/strain and bile-acid interventions reduce mouse calorie absorption; human observational and small ketogenic-diet studies show concordant associations.", "[35] P.distasonis improves ob/ob and high-fat mouse phenotypes; succinate plus secondary bile acids recapitulate metabolic benefits.", "[36] B.vulgatus/cholic acid and epithelial Tph1 contrasts implicate a microbe-metabolite-serotonin axis in lipid absorption and high-fat adiposity.", "[37] 2026 low-protein diet browning defect in germ-free mice is rescued by defined consortia; bile-acid/FXR and ammonia/FGF21 axes are nonredundant.", "[40] Microbial imidazole propionate is enriched in T2D material and impairs mouse glucose/insulin signalling through p38gamma/p62/mTORC1.", "[41] Third-trimester community differs from first trimester and transfers more adiposity/insulin insensitivity to germ-free mice.", "[42] Gpr41loss lowers adiposity in conventional and defined Bt/M.smithii-colonized mice despite similar chow intake, with transit/PYY/energy-harvest links.", "[45] Continuous LPS infusion increases fat/weight and liver insulin resistance; CD14mutants resist many LPS/high-fat phenotypes.", "[46] Live Akkermansia reduces high-fat fat gain and barrier/inflammatory abnormalities; heat-killed preparation was ineffective in this study.", "[47] Antibiotics lower endotoxemia, adiposity and inflammation in high-fat/obob mice; CD14deletion partly mimics the phenotype.", "[48] Maternal microbial SCFAs signal through embryonic GPR41/43 and affect later offspring metabolic susceptibility.", "[49] Acetylated cellulose limits body-mass gain through microbiota-dependent host-accessible sugar depletion and altered oxidation.", "[52] Urinary hippurate associates with human diet/metabolic state; chronic infusion improves glucose tolerance/insulin secretion in high-fat mice.", "[64] Germ-free Western-diet protection is lost with Fiafdeletion; AMPK/fatty-acid oxidation supports complementary host mechanisms.", "[67] GPR43loss/OE effects disappear with germ-free/antibiotic conditions; conventionalization and acetate rescue restore receptor-dependent fat effects.", "[68] Cold-community transfer drives browning/fat loss followed by absorptive compensation; Akk co-transfer diminishes intestinal adaptation." ], "what_would_cross_it": "To reach Η, reproduce narrowed strain/factor rescue across independent facilities with diet, cage, host background and handling controls; do not combine different pathways into one universal strain mechanism." }, { "subclaim_id": "SC2", "threshold": "Δ", "requirement_quoted": "Requires a transfer paradigm or causal perturbation in vivo.", "satisfied": "yes", "supporting_evidence": [ "[3] Human heritable Christensenellaceae associate with low BMI; cultured C.minuta amendment reduces recipient mouse weight gain.", "[9] GutBugs randomized 87 adolescents: BMI-SDS primary and total-fat percentage null; android/gynoid ratio lower at6/12/26 weeks.", "[11] Randomized lean versus autologous FMT improved six-week clamp insulin sensitivity in metabolic-syndrome men.", "[12] Turicibacter and purified bacterial lipids suppress host ceramides/fat uptake and obesity; dietary fat reduces colonization and continuous dosing restores benefit.", "[16] 2019 live/pasteurized Akk pilot improved selected metabolic measures;40enrolled32 completed; weight/fat changes were nonsignificant nearP=.09.", "[17] Pasteurization and Amuc1100/TLR2-linked protein partly recapitulate metabolic/fat benefits in mice; preliminary human safety was reported.", "[19] Repeated FMT in 61 obese T2D adults improved24 week donor engraftment, the primary endpoint; combined lifestyle arm had lipid/liver-stiffness changes.", "[21] Ba8145 original Methods/Results report live-cell BMI and killed-cell waist-related between-placebo benefits;126 received intervention of 135 reported participants.", "[23] 75-person BBr60 plus common dietary guidance trial reports greater weight/BMI reduction and metabolic/taxa changes than placebo.", "[24] L.rhamnosus formulation with prebiotics had an overall ITT weight null but treatment-by-sex interaction; women showed more weight/fat loss over24 weeks.", "[25] 2025GutBugs4 year follow-up found lower waist and body-fat percentage among 55returnees, with persistent donor strains and nonsignificant BMI difference.", "[26] 20healthy young men on a common high-fat1000 kcal-surplus diet gained less DXA fat and weight with VSL3 than placebo after4 weeks.", "[28] 631obese374control cohort associates Megamonas with obesity; M.rupellensis and heterologous iolG expression promote mouse lipid absorption, with myo-inositol functional support.", "[34] Microbial BSH/strain and bile-acid interventions reduce mouse calorie absorption; human observational and small ketogenic-diet studies show concordant associations.", "[38] Inpatient crossover feeding plus blinded vancomycin intervention met primary stool-energy-loss endpoints in 25 completers.", "[41] Third-trimester community differs from first trimester and transfers more adiposity/insulin insensitivity to germ-free mice.", "[43] Donor-characteristic FMT contrast in 22metabolic-syndrome men found worsened clamp sensitivity with metabolic-syndrome donors and bile/immune changes.", "[53] 2026 pasteurized-Akk RCT 90 people reports primary24 week weight regain1.2vs3.2 kg(P=.012) after successful low-energy-diet loss.", "[54] Lean-donor FMT improves six-week insulin sensitivity in selected baseline communities, with no metabolic effect at18 weeks.", "[56] 70-person FMT/fiber factorial reports six-week HOMA improvement in FMT-low-fermentable arm.", "[61] Propionate ester reduces threshold-defined weight-gain events and secondary intra-abdominal-fat distribution; acute appetite/hormone perturbation works.", "[63] Seven-day vancomycin versus amoxicillin changes microbes/bile acids and worsens peripheral clamp sensitivity in 20 men.", "[65] Rinott aFMT had overall primary regain null(P=.28), but green-Mediterranean interaction(P=.03) and diet-specific benefit(P=.02); Methods confirmITT90 with one imputation.", "[68] Cold-community transfer drives browning/fat loss followed by absorptive compensation; Akk co-transfer diminishes intestinal adaptation." ], "what_would_cross_it": "" }, { "subclaim_id": "SC2", "threshold": "Ε", "requirement_quoted": "Requires context-specific causal effect with defined limits. A transferable phenotype exists, but microbial identity or generalizability remains incomplete.", "satisfied": "no", "supporting_evidence": [ "[3] Human heritable Christensenellaceae associate with low BMI; cultured C.minuta amendment reduces recipient mouse weight gain.", "[9] GutBugs randomized 87 adolescents: BMI-SDS primary and total-fat percentage null; android/gynoid ratio lower at6/12/26 weeks.", "[11] Randomized lean versus autologous FMT improved six-week clamp insulin sensitivity in metabolic-syndrome men.", "[12] Turicibacter and purified bacterial lipids suppress host ceramides/fat uptake and obesity; dietary fat reduces colonization and continuous dosing restores benefit.", "[16] 2019 live/pasteurized Akk pilot improved selected metabolic measures;40enrolled32 completed; weight/fat changes were nonsignificant nearP=.09.", "[17] Pasteurization and Amuc1100/TLR2-linked protein partly recapitulate metabolic/fat benefits in mice; preliminary human safety was reported.", "[19] Repeated FMT in 61 obese T2D adults improved24 week donor engraftment, the primary endpoint; combined lifestyle arm had lipid/liver-stiffness changes.", "[21] Ba8145 original Methods/Results report live-cell BMI and killed-cell waist-related between-placebo benefits;126 received intervention of 135 reported participants.", "[23] 75-person BBr60 plus common dietary guidance trial reports greater weight/BMI reduction and metabolic/taxa changes than placebo.", "[24] L.rhamnosus formulation with prebiotics had an overall ITT weight null but treatment-by-sex interaction; women showed more weight/fat loss over24 weeks.", "[25] 2025GutBugs4 year follow-up found lower waist and body-fat percentage among 55returnees, with persistent donor strains and nonsignificant BMI difference.", "[26] 20healthy young men on a common high-fat1000 kcal-surplus diet gained less DXA fat and weight with VSL3 than placebo after4 weeks.", "[28] 631obese374control cohort associates Megamonas with obesity; M.rupellensis and heterologous iolG expression promote mouse lipid absorption, with myo-inositol functional support.", "[34] Microbial BSH/strain and bile-acid interventions reduce mouse calorie absorption; human observational and small ketogenic-diet studies show concordant associations.", "[38] Inpatient crossover feeding plus blinded vancomycin intervention met primary stool-energy-loss endpoints in 25 completers.", "[41] Third-trimester community differs from first trimester and transfers more adiposity/insulin insensitivity to germ-free mice.", "[43] Donor-characteristic FMT contrast in 22metabolic-syndrome men found worsened clamp sensitivity with metabolic-syndrome donors and bile/immune changes.", "[53] 2026 pasteurized-Akk RCT 90 people reports primary24 week weight regain1.2vs3.2 kg(P=.012) after successful low-energy-diet loss.", "[54] Lean-donor FMT improves six-week insulin sensitivity in selected baseline communities, with no metabolic effect at18 weeks.", "[56] 70-person FMT/fiber factorial reports six-week HOMA improvement in FMT-low-fermentable arm.", "[61] Propionate ester reduces threshold-defined weight-gain events and secondary intra-abdominal-fat distribution; acute appetite/hormone perturbation works.", "[63] Seven-day vancomycin versus amoxicillin changes microbes/bile acids and worsens peripheral clamp sensitivity in 20 men.", "[65] Rinott aFMT had overall primary regain null(P=.28), but green-Mediterranean interaction(P=.03) and diet-specific benefit(P=.02); Methods confirmITT90 with one imputation.", "[68] Cold-community transfer drives browning/fat loss followed by absorptive compensation; Akk co-transfer diminishes intestinal adaptation." ], "what_would_cross_it": "For Ε, confirm the bounded human adiposity effect in a prespecified population with fat-primary ITT analysis, validated functional exposure, dietary controls and reproducibility; use mediation and inactive-factor comparisons to narrow mechanism rather than as a prerequisite for giving randomized efficacy credit." }, { "subclaim_id": "SC3", "threshold": "Δ", "requirement_quoted": "Requires a transfer paradigm or causal perturbation in vivo.", "satisfied": "no", "supporting_evidence": [ "[9] GutBugs randomized 87 adolescents: BMI-SDS primary and total-fat percentage null; android/gynoid ratio lower at6/12/26 weeks.", "[11] Randomized lean versus autologous FMT improved six-week clamp insulin sensitivity in metabolic-syndrome men.", "[16] 2019 live/pasteurized Akk pilot improved selected metabolic measures;40enrolled32 completed; weight/fat changes were nonsignificant nearP=.09.", "[19] Repeated FMT in 61 obese T2D adults improved24 week donor engraftment, the primary endpoint; combined lifestyle arm had lipid/liver-stiffness changes.", "[23] 75-person BBr60 plus common dietary guidance trial reports greater weight/BMI reduction and metabolic/taxa changes than placebo.", "[25] 2025GutBugs4 year follow-up found lower waist and body-fat percentage among 55returnees, with persistent donor strains and nonsignificant BMI difference.", "[26] 20healthy young men on a common high-fat1000 kcal-surplus diet gained less DXA fat and weight with VSL3 than placebo after4 weeks.", "[33] PAHSA-treated community transfers insulin sensitivity on high-fat diet; Bt reduces adiposity in female mice, partly dependent on sex hormones.", "[38] Inpatient crossover feeding plus blinded vancomycin intervention met primary stool-energy-loss endpoints in 25 completers.", "[40] Microbial imidazole propionate is enriched in T2D material and impairs mouse glucose/insulin signalling through p38gamma/p62/mTORC1.", "[43] Donor-characteristic FMT contrast in 22metabolic-syndrome men found worsened clamp sensitivity with metabolic-syndrome donors and bile/immune changes.", "[52] Urinary hippurate associates with human diet/metabolic state; chronic infusion improves glucose tolerance/insulin secretion in high-fat mice.", "[54] Lean-donor FMT improves six-week insulin sensitivity in selected baseline communities, with no metabolic effect at18 weeks.", "[56] 70-person FMT/fiber factorial reports six-week HOMA improvement in FMT-low-fermentable arm.", "[61] Propionate ester reduces threshold-defined weight-gain events and secondary intra-abdominal-fat distribution; acute appetite/hormone perturbation works.", "[63] Seven-day vancomycin versus amoxicillin changes microbes/bile acids and worsens peripheral clamp sensitivity in 20 men." ], "what_would_cross_it": "In the same prespecified intervention show a positive fat endpoint, temporally ordered mediator engagement and a controlled mechanistic link, instead of substituting insulin or inflammation for fat." } ], "generalization_check": { "generalization_tested": "yes", "context_boundary_mapped": "yes", "internal_negative_controls": [ "FMT-TRIM primary clamp and fat/weight nulls despite engraftment [55]", "B420 ITT fat-primary null versus PP/posthoc signals [22]", "Live-Akk2025 whole-trial null versus baseline subgroup [5]", "Propionate mean-weight/total-adipose null and larger iPREVENT weight/fat null [61-62]", "Germ-free C3H/high-fat obesity counterexample [60]", "Mouse depletion glucose benefit without adiposity change [14]" ], "note": "Diet, sex, baseline metabolic status, developmental setting, strain and formulation are available before outcomes and map genuine boundaries. Low-baseline-Akk groups could be defined prospectively, but this review has not verified subgroup pre-specification/interaction in the2025paper. HOMA responder groups, core/noncore selection and compliant PP samples do not redefine the human claim. Positive weight maintenance and fat distribution are retained as their measured outcomes; neither is relabelled total fat loss. Several primary human trials are null, so general human configuration causation is incomplete." }, "falsification_patterns_met": [ { "pattern": "Target engagement without nominated outcome", "evidence": "FMT-TRIM engraftment occurred without a significant fat or weight effect [55]; synbiotic taxa changed without composition benefit [20].", "downgrade_applied": false }, { "pattern": "Removal does not prevent phenotype generally", "evidence": "One germ-free diet/strain setting developed more adiposity [60]; short human antibiotics changed ecology without clinically relevant adiposity effects [58].", "downgrade_applied": false }, { "pattern": "Larger longer test fails primary replication", "evidence": "iPREVENT did not reproduce a mean-weight prevention effect and had a fat-mass null [62], while the earlier trial itself had a mean-weight null [61].", "downgrade_applied": false } ], "pitfalls_flagged": [ { "pitfall": "Mouse transfer treated as human causality", "where": "Human donors remain mouse recipient experiments [2-3,28]." }, { "pitfall": "Primary null replaced by selected success", "where": "B420PP/posthoc, whole-trial live-Akk null, and aFMT dietary interaction require distinct reporting [5,22,65-66]." }, { "pitfall": "Within-arm significance treated as interaction", "where": "Mocanu abstract emphasizes within-arm HOMA; original randomized contrast is not independently verified [56]." }, { "pitfall": "Body weight or fat distribution renamed total fat", "where": "GutBugs, propionate and pasteurized-Akk endpoints differ [9,25,53,61]." }, { "pitfall": "Nonliving product efficacy equated with living configuration", "where": "Heat-killed/pasteurized bacteria and purified protein/lipids can work without community engraftment [12,17,21,53]." }, { "pitfall": "Selected long-term returnees treated as complete randomized follow-up", "where": "GutBugs4 year is unblinded,63%recaptured and clinically multiplicity-unadjusted [25]." }, { "pitfall": "Microbial metabolite sign assumed universal", "where": "GPR41, GPR43, cold compensation and commensal carbohydrate consumption have distinct directions [42,49,67-68]." } ], "causal_tally_audit": { "tally_claimed_by_document": 46, "tally_after_audit": 46, "items_rejected": [ "Null and negative contrasts are discriminators, not positive threshold crossings. Reports and replications are not independent causal lines.", "Positive flags describe a scoped phenotype/mediator intervention, including animal or non-adiposity endpoints; they are not68 independent causal lines or68 human fat successes. FMT crude-community evidence is at most Moderate specificity even when the trial design is sound. Randomized-cohort follow-up retains a positive observed contrast with attrition/multiplicity limits." ] }, "steelman": { "case_one_rung_higher": "The strongest case for Ε is a controlled human fat-gain experiment [26], sex- and diet-specific adiposity responses [21,24,65], repeated FMT fat-distribution signals including4 year fat percentage [9,25], and a new primary weight-maintenance success [53]. Defined mouse functions make a merely associative interpretation untenable.", "case_one_rung_lower": "The strongest case for Γ is that prominent FMT and fat-primary trials are null, positive clinical effects are often secondary or selected, and a pasteurized product does not prove live-community causation [5,16,20,22,55,58,61-62]. Mouse transfer alone cannot establish human scope.", "which_rejected": "Retain Δ for the prespecified human-contribution gate. Reject Γ as a blanket grade that would erase controlled human fat accumulation evidence; reject Ε for the broad mechanism because reproducible specific human adiposity attribution and generalization remain incomplete. Animal SC1Ζ is retained separately, while the insulin-to-fat inference SC3 remains Γ.", "blocking_cap_threshold_or_missing_experiment": "Missing experiment: Randomize a prespecified human obesity population to a defined live strain/consortium, an otherwise matched inactive microbial preparation and placebo, under matched dietary exposure. Use a registered fat-mass primary ITT endpoint over6-12 months, separate maintenance from initial loss, and measure strain/function exposure, energy intake/loss, expenditure and candidate mediators longitudinally. Confirm the same function with subtraction/addition and rescue in two independent recipient facilities; replicate clinical effects in a separate cohort." }, "final_score": { "hsef_level": "Δ", "hsef_descriptor": "First field-valid causal perturbation crossed", "confidence": "Moderate", "confidence_rationale": "68 primary reports with 10 selected partial-body examinations; density, heterogeneous controls and incomplete access set the confidence, not correctness.", "rests_on_non_peer_reviewed_work": false, "rationale": "The preregistered scope-matched human-contribution gate SC2 yields Δ / Moderate. Selected controlled human adiposity contrasts cross the in-vivo causal boundary, so a blanket Γ on mouse-to-human inference is not reapplied to the convergent human set. SC1 reaches scoped Ζ for animal transmissibility/rescue; SC3 remains Γ for the endpoint-substitution inference. Weakest-link sensitivity is Γ, primary-subclaim and scope-matched Δ. A stronger universal or primary human-driver reading would remain Γ; that is a separate burden, not a requirement silently added to the registered contribution gate." }, "role_of_mechanism": { "classification": "reinforcing / stabilizing factor", "derivation_step_matched": 5, "derivation": "The human interventions can modify fat gain or weight maintenance under upstream diet/host conditions. They do not establish universal necessity, initiation and rate limitation together. A changed microbial marker may also be downstream of diet or host physiology, but the demonstrated intervention effects preclude classifying the entire mechanism as a passive epiphenomenon.", "tournament_used_as_tiebreaker": false, "note": "Derived from causal direction, not tournament rank." }, "extended_scoring_MSD": { "momentum": { "value": "Mechanistic only", "artifact": "The 2026 primary weight-maintenance trial [53] and 2024-2026 strain/gene/lipid/consortium studies [12,28,34,36-37,49] improve experimental specificity; new results include context and endpoint limits.", "justification": "The 2026 primary weight-maintenance trial [53] and 2024-2026 strain/gene/lipid/consortium studies [12,28,34,36-37,49] improve experimental specificity; new results include context and endpoint limits." }, "stability": { "value": "Stable", "trigger": "No verified pending trial is used to forecast a score change. Independently replicated fat-primary, strain-function and mediation trials could change the level; their results are not assumed.", "justification": "No verified pending trial is used to forecast a score change. Independently replicated fat-primary, strain-function and mediation trials could change the level; their results are not assumed." }, "divergence": { "implied_level": null, "implied_level_basis": "No single field-implied level is defensible from conflicting framings.", "assessed_level": "Δ", "gap_in_rungs": null, "value": "Contested", "justification": "No manufactured field consensus or arithmetic gap." }, "calibration_note": "M/S/D never modify HSEF level or confidence." }, "change_record": { "applies": false, "prior_level": "Ranking categorical verdict visible; no prior letter used as a target", "prior_confidence": null, "prior_source": null, "derived_before_consulting_prior": false, "new_level": "Δ", "direction": "newly assigned", "what_moved_it": "Fresh primary evidence appraisal; not blinded.", "divergence_from_other_reviewers": null }, "proposed_decisive_experiments": [ { "name": "Registered boundary experiment", "experiment": "Randomize a prespecified human obesity population to a defined live strain/consortium, an otherwise matched inactive microbial preparation and placebo, under matched dietary exposure. Use a registered fat-mass primary ITT endpoint over6-12 months, separate maintenance from initial loss, and measure strain/function exposure, energy intake/loss, expenditure and candidate mediators longitudinally. Confirm the same function with subtraction/addition and rescue in two independent recipient facilities; replicate clinical effects in a separate cohort.", "readout": "DXA total fat mass and validated visceral fat, with distinct body weight, energy absorption, clamp and hormone outcomes; predefined between-arm contrasts and mediator timing", "critical_control": "Allocation concealment, blinding, full ITT/missing-data sensitivity, inactive-factor control, stable medications, stratified baseline microbiome/sex/diet, exposure/engraftment measures, clinical multiplicity and cage/diet-batch controls", "supporting_result": "A prespecified clinically meaningful fat difference with confirmed microbial functional exposure and independently replicated causal pathway, beyond matched dietary exposure without assuming unchanged appetite is required", "falsifying_result": "Adequate exposure with a precise fat-primary null across prespecified contexts, inactive product matching live efficacy without the nominated function, or loss of the effect after dietary/host and missing-data controls" } ], "knowledge_gaps": [ { "name": "Gap 1", "statement": "Replicate fat-primary human outcomes with prespecified between-arm contrasts rather than secondary, compliance-selected or response-defined analyses.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 2", "statement": "Separate living-community changes from the activity of nonliving cells, purified proteins or bacterial lipids using matched inactive-component controls.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 3", "statement": "Validate baseline taxon/function treatment selectors prospectively with interaction tests; within-arm significance and posthoc responders do not establish selection.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 4", "statement": "Quantify human energy intake/loss, expenditure and adiposity over time to test compensation and distinguish mechanism from short-term stool calorimetry.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 5", "statement": "Replicate strain/substrate rescue across facilities with cage, vendor, diet batch, host background and handling controls; do not universalize SCFA direction.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 6", "statement": "Complete original Methods, protocols, supplements and correction checks for newly positive clinical trials, including2026Akk fat outcomes and allocation/attrition; audit commercial conflicts and shared cohorts.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 7", "statement": "Maintain long-term blinded follow-up with attrition sensitivity and multiplicity control; GutBugs4 year findings need independent replication.", "relevance": "Limits mechanism identification or scope." } ], "review_metadata": { "review_date": "2026-10-05", "reviewer": "Codex", "evidence_base_note": "68 primary reports; cutoff 2026-10-05; bounded critical review, not exhaustive systematic review.", "literature_tools_available": true, "literature_tools_note": "Life Sciences Literature PubMed/Europe PMC; signed-in Consensus browser discovery and indexed full-text extraction; independent checks against original sections. Zero Consensus API calls.", "skill_version": "5.3", "validator_run": "exact archived v5.3 validator 2.3; see validator.txt", "validator_warnings_addressed": "Phenomenon entry was restated as the preregistered causal claim. No real phenomenon is labelled refuted; warning is explicitly justified.", "consensus_consistency_audit": "2026-10-09; supplementary provenance/source reconciliation; original grading retained; prior grades visible." }, "is_calibration_entry": { "value": false, "entry_role": "not_calibration", "blind_graded": null, "completed_blinded_calibration": false, "expected_band_sealed_at": "", "target_sha256": "", "target_authorship": "not applicable", "target_author_saw_review": null, "future_run_status": "not prepared", "unblinded_reason": "Ranking categorical verdict and index guidance were visible. No completed blinded calibration claimed." }, "upper_ladder_check": { "final_level_below_zeta": true, "equivalents_considered": [ { "kind": "mendelian_randomization", "available": false, "why_not_sufficient": "Defined strain/consortium rescue plus receptor/gene interventions across distinct mouse contexts carry SC1 to Ζ. Human randomized adiposity and primary weight-maintenance trials are field-valid clinical perturbations considered on their own terms; crude transfer, null primary results, endpoint differences and unverified functional mediation prevent a narrowed reproducible SC2Ζ mechanism. Natural experiments and dose/eradication equivalents were considered but no examined human obesity set meets that burden. Higher levels remain live; an unethical human obesity-induction experiment is not demanded." }, { "kind": "natural_experiment", "available": false, "why_not_sufficient": "Defined strain/consortium rescue plus receptor/gene interventions across distinct mouse contexts carry SC1 to Ζ. Human randomized adiposity and primary weight-maintenance trials are field-valid clinical perturbations considered on their own terms; crude transfer, null primary results, endpoint differences and unverified functional mediation prevent a narrowed reproducible SC2Ζ mechanism. Natural experiments and dose/eradication equivalents were considered but no examined human obesity set meets that burden. Higher levels remain live; an unethical human obesity-induction experiment is not demanded." }, { "kind": "dose_response_across_populations", "available": false, "why_not_sufficient": "Defined strain/consortium rescue plus receptor/gene interventions across distinct mouse contexts carry SC1 to Ζ. Human randomized adiposity and primary weight-maintenance trials are field-valid clinical perturbations considered on their own terms; crude transfer, null primary results, endpoint differences and unverified functional mediation prevent a narrowed reproducible SC2Ζ mechanism. Natural experiments and dose/eradication equivalents were considered but no examined human obesity set meets that burden. Higher levels remain live; an unethical human obesity-induction experiment is not demanded." }, { "kind": "withdrawal_rechallenge", "available": false, "why_not_sufficient": "Defined strain/consortium rescue plus receptor/gene interventions across distinct mouse contexts carry SC1 to Ζ. Human randomized adiposity and primary weight-maintenance trials are field-valid clinical perturbations considered on their own terms; crude transfer, null primary results, endpoint differences and unverified functional mediation prevent a narrowed reproducible SC2Ζ mechanism. Natural experiments and dose/eradication equivalents were considered but no examined human obesity set meets that burden. Higher levels remain live; an unethical human obesity-induction experiment is not demanded." }, { "kind": "therapeutic_perturbation_hard_endpoint", "available": true, "why_not_sufficient": "Defined strain/consortium rescue plus receptor/gene interventions across distinct mouse contexts carry SC1 to Ζ. Human randomized adiposity and primary weight-maintenance trials are field-valid clinical perturbations considered on their own terms; crude transfer, null primary results, endpoint differences and unverified functional mediation prevent a narrowed reproducible SC2Ζ mechanism. Natural experiments and dose/eradication equivalents were considered but no examined human obesity set meets that burden. Higher levels remain live; an unethical human obesity-induction experiment is not demanded." } ], "convergence_present": true, "cap_reapplied_to_convergent_set": false }, "provenance_header": { "sources_total": 68, "claims_total": 72, "claims_verified": 72, "claims_unverified": 0, "claims_contradicted": 0, "tier_a_sources": 68, "generated_by": "Codex; HSEF v5.3", "gate_passed": true }, "claims": [ { "id": "C1", "text": "Obese-donor community transfers greater fat accumulation and energy-harvest capacity to germ-free recipients. Crude communities and exceptional recipients do not identify a universal human obesity configuration or exclude diet interaction.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 1 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C2", "text": "Discordant-twin fecal communities and cultured collections transfer adiposity; lean-community invasion rescues in a diet-dependent manner. Human donors are not human causal recipients; saturated-fat/low-produce diet blocks rescue and donor/cage dependence limits generality.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 2 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C3", "text": "Human heritable Christensenellaceae associate with low BMI; cultured C.minuta amendment reduces recipient mouse weight gain. Causal attribution applies to mouse amendment; the human twin relation is observational and weight gain is not a human treatment endpoint.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 3 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C4", "text": "Microbial control of circadian NFIL3 links innate immune signalling to intestinal lipid absorption and body composition. A host pathway in mice does not demonstrate independent human adiposity causation; circadian and dietary conditions matter.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 4 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C5", "text": "The 58-person live-Akkermansia RCT found no whole-group between-treatment weight or HbA1c difference; low-baseline-Akk subgroup had colonization and fat/weight signals. Abstract-only subgroup pre-specification, interaction and multiplicity are unresolved; within-arm significance is not a between-arm interaction.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 5 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C6", "text": "Conventionalization increases body fat despite lower intake; Fiaf knockout experiments implicate host lipid-storage regulation. Germ-free development and host-genotype manipulation limit human inference; later diet/strain counterexperiments constrain universality.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 6 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C7", "text": "Emulsifier-associated communities transfer inflammation/metabolic phenotype; germ-free contrasts support a microbial contribution. Crude transfer has at most Moderate specificity; exposure may have additional host effects and linked erratum27144359 was not audited in full.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 7 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C8", "text": "154 people show shared microbial gene functions and obesity-associated diversity, phylum and pathway differences. Families and diet share determinants; association does not establish direction, a diagnostic phylum ratio or a human fat-producing mechanism.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 8 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C9", "text": "GutBugs randomized 87 adolescents: BMI-SDS primary and total-fat percentage null; android/gynoid ratio lower at6/12/26 weeks. Original Methods use no clinical multiplicity adjustment; secondary fat distribution is not total fat loss, and metabolic-syndrome resolution is post hoc.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 9 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph1, 1:Methods:paragraph5, 1:Methods:paragraph6, 1:Methods:paragraph7, 1:Methods:paragraph9, 1:Methods:paragraph10, 2:Results:paragraph0, 2:Results:paragraph4, 2:Results:paragraph5, 2:Results:paragraph8. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C10", "text": "Epithelial HDAC3 integrates microbial/circadian cues, induces Cd36/lipid uptake and promotes diet-induced obesity. Host transcriptional perturbation supports a mouse mechanism; human adiposity and effect magnitude were not established.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 10 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C11", "text": "Randomized lean versus autologous FMT improved six-week clamp insulin sensitivity in metabolic-syndrome men. Insulin sensitivity is not fat accumulation; crude FMT lacks strain attribution and the linked unspecified erratum requires separate audit.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 11 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C12", "text": "Turicibacter and purified bacterial lipids suppress host ceramides/fat uptake and obesity; dietary fat reduces colonization and continuous dosing restores benefit. The human metagenomic relation is observational; diet-dependent microbial protection does not establish a human pro-obesity configuration.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 12 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C13", "text": "Jejunal microbiota from high-fat donors increases recipient lipid absorption even on low-fat diet; conditioned media induce epithelial uptake genes. Recipient absorption and organoid activity are not a quantified human body-fat effect; crude transfer specificity remains limited.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 13 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C14", "text": "Depletion improves glucose tolerance and insulin sensitivity without changing adiposity, alongside SCFA/bile changes. Broad antibiotics have host effects; glucose improvement explicitly cannot substitute for fat loss.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 14 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C15", "text": "FXR genotype and germ-free/conventional contrasts change diet-induced adiposity; donor community transfers phenotype. Host receptor dependence and transfer do not locate an invariant microbial cause of human obesity.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 15 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C16", "text": "2019 live/pasteurized Akk pilot improved selected metabolic measures;40enrolled32 completed; weight/fat changes were nonsignificant nearP=.09. Body fat used bioimpedance, not DXA; original text and abstract differ on the fat comparator, but neither demonstrates significant fat loss; calorie/activity detail and baseline insulin balance limited.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 16 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 0:Online Methods:paragraph0, 0:Online Methods:paragraph1, 0:Online Methods:paragraph2, 0:Online Methods:paragraph4, 0:Online Methods:paragraph5, 0:Online Methods:paragraph6, 0:Online Methods:paragraph13, 0:Online Methods:paragraph15, 7:Main text (unsectioned body paragraphs):paragraph1, 7:Main text (unsectioned body paragraphs):paragraph2, 7:Main text (unsectioned body paragraphs):paragraph3, 7:Main text (unsectioned body paragraphs):paragraph13, 7:Main text (unsectioned body paragraphs):paragraph14, 7:Main text (unsectioned body paragraphs):paragraph4, 7:Main text (unsectioned body paragraphs):paragraph5, 7:Main text (unsectioned body paragraphs):paragraph6, 7:Main text (unsectioned body paragraphs):paragraph7, 7:Main text (unsectioned body paragraphs):paragraph8, 7:Main text (unsectioned body paragraphs):paragraph9. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C17", "text": "Pasteurization and Amuc1100/TLR2-linked protein partly recapitulate metabolic/fat benefits in mice; preliminary human safety was reported. A bioactive nonliving component is not living-community engraftment; preliminary human volunteers belong to the later2019trial family.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 17 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C18", "text": "Obese metabolically uncompromised participants show donor-like engraftment/bile changes but no GLP1-area or BMI improvement. Safety was primary, small pilot; PubMed abstract has an implausible BMI-threshold typo, so exact eligibility needs original verification.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 18 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C19", "text": "Repeated FMT in 61 obese T2D adults improved24 week donor engraftment, the primary endpoint; combined lifestyle arm had lipid/liver-stiffness changes. Engraftment-primary success is not adiposity success; baseline comparisons and cointervention cannot establish independent FMT fat loss.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 19 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C20", "text": "Twenty-person synbiotic plus reduced-energy diet pilot changed beneficial taxa but not between-arm body mass, fat mass or composition. Small precision and combined diet limit exclusion of modest effects; taxa improvement is not a successful obesity endpoint.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 20 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C21", "text": "Ba8145 original Methods/Results report live-cell BMI and killed-cell waist-related between-placebo benefits;126 received intervention of 135 reported participants. MRI visceral-fat between-placebo contrasts are nonsignificant(P=.120/.086 for killed cells), despite significant within-baseline change; statistics/hierarchy in unread supplement and higher killed-arm fiber complicate interpretation; Akk correlation is not mediation.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 21 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Methods, 2:Results. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C22", "text": "B420factorial RCT randomized 225; ITT 209 fat-primary null; PP combination and post-unblinding factorial analyses positive. Original Methods confirm modified ITT/LOCF, Dunnett contrasts and posthoc PP factorial; selective compliance and reduced intake weaken direct microbial mediation; zonulin correlation is not barrier causation.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 22 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Materials and Methods:paragraph0, 1:Materials and Methods:paragraph5, 1:Materials and Methods:paragraph7, 1:Materials and Methods:paragraph15, 1:Materials and Methods:paragraph16, 1:Materials and Methods:paragraph17, 2:Results:paragraph0, 2:Results:paragraph1, 2:Results:paragraph4, 2:Results:paragraph5, 2:Results:paragraph7, 2:Results:paragraph10. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C23", "text": "75-person BBr60 plus common dietary guidance trial reports greater weight/BMI reduction and metabolic/taxa changes than placebo. Abstract-only fat outcomes, primary hierarchy and multiplicity remain unresolved; metabolomic correlation does not identify the mediator.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 23 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C24", "text": "L.rhamnosus formulation with prebiotics had an overall ITT weight null but treatment-by-sex interaction; women showed more weight/fat loss over24 weeks. Sex interaction retains scoped causal credit; formulation and restricted diet prevent isolating a strain-only mechanism, and sex-specific primary status remains to be audited.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 24 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C25", "text": "2025GutBugs4 year follow-up found lower waist and body-fat percentage among 55returnees, with persistent donor strains and nonsignificant BMI difference. Same trial family; unblinded after26 weeks,37%lost, no missing-data imputation and unadjusted clinical multiplicity; intervening diet/medication unknown.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 25 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph0, 1:Results:paragraph1, 1:Results:paragraph2, 1:Results:paragraph3, 1:Results:paragraph4, 1:Results:paragraph5, 1:Results:paragraph6, 1:Results:paragraph8, 1:Results:paragraph10, 1:Results:paragraph12, 1:Results:paragraph14, 1:Results:paragraph15, 2:Discussion:paragraph1, 2:Discussion:paragraph3, 3:Methods:paragraph0, 3:Methods:paragraph1, 3:Methods:paragraph2, 3:Methods:paragraph3, 3:Methods:paragraph17, 3:Methods:paragraph42, 3:Methods:paragraph43, 3:Methods:paragraph45, 3:Methods:paragraph46. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C26", "text": "20healthy young men on a common high-fat1000 kcal-surplus diet gained less DXA fat and weight with VSL3 than placebo after4 weeks. Direct controlled fat-accumulation contrast supports a bounded human contribution; small/short study, multiple-strain product and unverified engraftment limit mechanism/generalization.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 26 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C27", "text": "PREDICT1 links microbiome, habitual diet and standardized-meal metabolic responses in 1098 participants with external biomarker replication. Same-meal responses and prediction are not microbiome randomization; public cohorts may recur elsewhere and cannot become independent causal replications.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 27 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C28", "text": "631obese374control cohort associates Megamonas with obesity; M.rupellensis and heterologous iolG expression promote mouse lipid absorption, with myo-inositol functional support. The human portion is observational and the primary body unavailable; gene/strain perturbations narrow a mouse mechanism without demonstrating human treatment mediation.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 28 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C29", "text": "Immigration-associated microbial loss and Westernization track residence, generation and obesity, including19 people sampled before/after migration. Migration simultaneously changes food, environment and host exposures; longitudinal association does not isolate microbial causation of fat gain.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 29 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C30", "text": "Isocaloric Mediterranean diet altered microbes/metabolites and lowered cholesterol, the primary endpoint, in 82adults. Diet was randomized, not microbes; microbial/insulin covariance does not establish adiposity mediation or microbiome-independent weight control.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 30 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C31", "text": "1046 people show shared-household/diet/drug associations and modest host-genetic contribution to overall community variation; microbes improve phenotype prediction. Prediction and variance attribution do not establish direction, independence from all host physiology or causal fat accumulation.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 31 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C32", "text": "Low microbial gene richness associates with adiposity/metabolic inflammation and later weight gain in a Danish cohort. Temporal prediction reduces one timing ambiguity but does not randomize diet/host determinants or prove richness itself causal.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 32 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C33", "text": "PAHSA-treated community transfers insulin sensitivity on high-fat diet; Bt reduces adiposity in female mice, partly dependent on sex hormones. Effect differs by diet and sex; glucose improvement and female fat reduction must not be combined into universal human mediation; linked preprint is same study.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 33 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C34", "text": "Microbial BSH/strain and bile-acid interventions reduce mouse calorie absorption; human observational and small ketogenic-diet studies show concordant associations. Human diet intervention is not microbial-mediator randomization; bile-acid replacement does not alone prove the community configuration causes human fat gain.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 34 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C35", "text": "P.distasonis improves ob/ob and high-fat mouse phenotypes; succinate plus secondary bile acids recapitulate metabolic benefits. Model-specific rescue supports function rather than a universal abundance signature; isolated mediator effects on glucose are distinct from all fat endpoints.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 35 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C36", "text": "B.vulgatus/cholic acid and epithelial Tph1 contrasts implicate a microbe-metabolite-serotonin axis in lipid absorption and high-fat adiposity. Host epithelial and dietary dependencies are integral; human colonization and adiposity mediation are not established.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 36 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C37", "text": "2026 low-protein diet browning defect in germ-free mice is rescued by defined consortia; bile-acid/FXR and ammonia/FGF21 axes are nonredundant. Browning genes and dietary compensation are not all clinical fat outcomes; human donor selection is not a human causal trial; linked preprint excluded as duplicate.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 37 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C38", "text": "Inpatient crossover feeding plus blinded vancomycin intervention met primary stool-energy-loss endpoints in 25 completers. Human energy-harvest perturbation is real bounded evidence, but broad antibiotic effects and short timing do not quantify sustained adiposity or a specific microbial mediator.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 38 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C39", "text": "Animal versus plant diets rapidly alter microbial composition and expression, including bile-tolerant and foodborne microbes. Establishes diet-to-community responsiveness, not community-to-fat causation; transient detection is not durable functional colonization.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 39 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C40", "text": "Microbial imidazole propionate is enriched in T2D material and impairs mouse glucose/insulin signalling through p38gamma/p62/mTORC1. Glucose pathology is not adiposity; human metabolite and hepatic pathway associations do not independently establish human fat mediation.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 40 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C41", "text": "Third-trimester community differs from first trimester and transfers more adiposity/insulin insensitivity to germ-free mice. Normal host pregnancy remodels microbes upstream; adaptive physiology and crude cross-species transfer do not establish common human obesity initiation.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 41 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C42", "text": "Gpr41loss lowers adiposity in conventional and defined Bt/M.smithii-colonized mice despite similar chow intake, with transit/PYY/energy-harvest links. Host receptor, community and transit jointly determine effect; no quantified human fat contribution or universal SCFA direction follows.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 42 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C43", "text": "Donor-characteristic FMT contrast in 22metabolic-syndrome men found worsened clamp sensitivity with metabolic-syndrome donors and bile/immune changes. Two-week glucose effect is not fat accumulation; no neutral-placebo inference or defined mediator from crude donor material.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 43 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C44", "text": "Ob/ob mice have altered Firmicutes/Bacteroidetes despite shared diet and family comparisons. Leptin genotype precedes phenotype and microbial ecology; this observational contrast cannot establish microbial direction or phylum-ratio necessity.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 44 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C45", "text": "Continuous LPS infusion increases fat/weight and liver insulin resistance; CD14mutants resist many LPS/high-fat phenotypes. Artificial infusion and host knockout support a defined inflammatory axis, not endogenous human exposure magnitude or all insulin resistance.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 45 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C46", "text": "Live Akkermansia reduces high-fat fat gain and barrier/inflammatory abnormalities; heat-killed preparation was ineffective in this study. Heat-killing is not equivalent to later pasteurization; formulation/context matter, and human inverse abundance is associative.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 46 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C47", "text": "Antibiotics lower endotoxemia, adiposity and inflammation in high-fat/obob mice; CD14deletion partly mimics the phenotype. Antibiotic pleiotropy and shared investigative programme constrain specificity; no human fat or endogenous LPS mediation estimate.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 47 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C48", "text": "Maternal microbial SCFAs signal through embryonic GPR41/43 and affect later offspring metabolic susceptibility. Developmental maternal mechanism is distinct from adult recipient obesity and not directly generalized to human fat accumulation.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 48 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C49", "text": "Acetylated cellulose limits body-mass gain through microbiota-dependent host-accessible sugar depletion and altered oxidation. Mouse prebiotic substrate effect is diet-dependent; bacterial carbohydrate consumption can protect rather than increase host energy harvest.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 49 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C50", "text": "4198 people and243repeat samples identify drug/polypharmacy-associated community functions with initiation/cessation tracking. Confounder evidence is not obesity mechanism; treatment and disease indication share causes, and linked36610810erratum not fully audited.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 50 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C51", "text": "Diet and mouse strain explain substantial community shifts when high-fat obesity susceptibility is experimentally dissociated. Community changes need not track fat gain; indomethacin and genotype add effects and do not erase all microbial causality.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 51 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C52", "text": "Urinary hippurate associates with human diet/metabolic state; chronic infusion improves glucose tolerance/insulin secretion in high-fat mice. Host conjugation contributes to metabolite origin; glucose benefit is not direct human fat reduction or universal microbial mediation.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 52 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C53", "text": "2026 pasteurized-Akk RCT 90 people reports primary24 week weight regain1.2vs3.2 kg(P=.012) after successful low-energy-diet loss. Abstract plus publisher ancillary statements only: fat results, attrition and multiplicity unavailable; nonliving product benefit does not demonstrate living-community causation; company/patent conflicts disclosed.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 53 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C54", "text": "Lean-donor FMT improves six-week insulin sensitivity in selected baseline communities, with no metabolic effect at18 weeks. Metabolic responder stratification is not prevalidated adiposity selection; transient clamp effect is not sustained fat control.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 54 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C55", "text": "FMT-TRIM randomized 24; primary clamp null and secondary weight/fat mass null despite variable donor engraftment. Original Methods power only for large clamp effects; pilot null is not equivalence, donor strength differs and16SASVs cannot uniquely resolve all strains.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 55 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph1, 1:Methods:paragraph3, 1:Methods:paragraph6, 1:Methods:paragraph7, 2:Results:paragraph0, 2:Results:paragraph6, 2:Results:paragraph13, 2:Results:paragraph14, 2:Results:paragraph15, 2:Results:paragraph16, 2:Results:paragraph17. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C56", "text": "70-person FMT/fiber factorial reports six-week HOMA improvement in FMT-low-fermentable arm. Abstract chiefly reports within-armP=.02: significance versus other null arms is not a between-arm treatment effect; original contrasts and adiposity mediation unverified.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 56 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C57", "text": "Mocanu trial follow-up groups21responders8nonresponders; baseline taxa/engraftment correlate with HOMA response. Same family and response-defined subgroups; predictionAUC.70 is not external validation or new randomized human fat causation.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 57 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C58", "text": "57-obese-prediabetic-men antibiotic RCT changes communities/SCFA/bile but not clinically relevant energy harvest, insulin sensitivity or adipocyte size through8 weeks. Short broad intervention cannot falsify all configurations; null adipocyte size is not all total-fat endpoints, and correction completeness is limited.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 58 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C59", "text": "Inpatient energy-balance study in 12lean9 obese links nutrient load, stool energy and Firmicutes/Bacteroidetes, including an approximately150 kcal association. Dietary load changes microbes and absorption together; microbial proportions were not randomized and150 kcal is not a demonstrated sustained fat-gain cause.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 59 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C60", "text": "Germ-free C3Hmice gain more fat on one high-fat formula while Western diet behaves differently; Fiaf differences do not match universal protection. Diet/strain boundary challenges necessity and simple Fiaf universalization; does not negate positive mechanisms in other hosts or substrates.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 60 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C61", "text": "Propionate ester reduces threshold-defined weight-gain events and secondary intra-abdominal-fat distribution; acute appetite/hormone perturbation works. Original24 week mean weight differenceP=.099 and total-adipose difference null;49/60 completers and32composition data; ester delivery is not randomized living community.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 61 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Methods:paragraph3, 1:Methods:paragraph4, 1:Methods:paragraph5, 1:Methods:paragraph7, 1:Methods:paragraph9, 2:Results:paragraph1, 2:Results:paragraph5, 2:Results:paragraph6, 2:Results:paragraph9, 2:Results:paragraph10, 2:Results:paragraph13. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C62", "text": "iPREVENT270 randomized:12 month primary weight difference1.02kgCI-.37to2.41 null; secondary fat-mass difference.07kgCI-1.07to1.21 null. Original model used256 with any follow-up,226at12 months; adherence and low control weight gain constrain exposure/generalization, not permission to declare overall efficacy.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 62 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph1, 1:Methods:paragraph3, 1:Methods:paragraph4, 1:Methods:paragraph6, 1:Methods:paragraph8, 1:Methods:paragraph11, 1:Methods:paragraph12, 1:Methods:paragraph13, 1:Methods:paragraph22, 1:Methods:paragraph23, 1:Methods:paragraph28, 1:Methods:paragraph29, 1:Methods:paragraph30, 2:Results:paragraph0, 2:Results:paragraph4, 2:Results:paragraph5, 2:Results:paragraph10, 2:Results:paragraph14, 2:Results:paragraph15, 2:Results:paragraph16, 2:Results:paragraph18. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C63", "text": "Seven-day vancomycin versus amoxicillin changes microbes/bile acids and worsens peripheral clamp sensitivity in 20 men. Active-antibiotic comparator and short treatment do not isolate a microbial mediator or establish fat gain.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 63 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C64", "text": "Germ-free Western-diet protection is lost with Fiafdeletion; AMPK/fatty-acid oxidation supports complementary host mechanisms. Diet/strain counterstudy limits universal Fiaf or microbiota necessity; protection is not endogenous human causal weight evidence.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 64 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C65", "text": "Rinott aFMT had overall primary regain null(P=.28), but green-Mediterranean interaction(P=.03) and diet-specific benefit(P=.02); Methods confirmITT90 with one imputation. Diet-specific weight result is not uniform FMT or total-fat success; original protocol/supplement pre-specification not independently audited; crude transfer remains nonspecific.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 65 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: PMC original author manuscript: Methods/Statistical analysis and Results/Weight regain, lines300-305,335-342,396-413. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C66", "text": "DIRECT-PLUS secondary analysis associates low-core/high-noncore community change with aFMT weight maintenance. Same trial family, response-related multivariate subgroup and taxa selection; not independent efficacy replication or prospective validation.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 66 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C67", "text": "GPR43loss/OE effects disappear with germ-free/antibiotic conditions; conventionalization and acetate rescue restore receptor-dependent fat effects. Original strains differ between KO and OE backgrounds; lifelong manipulation and receptor/tissue specificity limit universal SCFA or human obesity inference.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 67 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 0:Results:paragraph0, 0:Results:paragraph1, 0:Results:paragraph2, 0:Results:paragraph3, 0:Results:paragraph4, 0:Results:paragraph5, 0:Results:paragraph6, 0:Results:paragraph7, 0:Results:paragraph8, 1:Discussion:paragraph4, 1:Discussion:paragraph5, 1:Discussion:paragraph6, 2:Methods:paragraph0, 2:Methods:paragraph1, 9:Main text (unsectioned body paragraphs):paragraph2, 9:Main text (unsectioned body paragraphs):paragraph3. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "C68", "text": "Cold-community transfer drives browning/fat loss followed by absorptive compensation; Akk co-transfer diminishes intestinal adaptation. Physiological demand, substrate and compensation change the sign/magnitude; a protective transfer is not a universal human fat-producing configuration.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 68 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-05", "note": "" }, { "id": "CSC1", "text": "Transfer, cultured-community/strain amendment and rescue repeatedly move recipient adiposity, with defined functions and host-receptor tests addressing distinct errors [1-4,6-7,10,12-15,17,28,33-37,41-42,45-49,64,67-68]. The broad defined-recipient claim reaches Ζ across distinct mechanisms; this does not promote every individual strain or infer human causality.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 1, 2, 3, 4, 6, 7, 10, 12, 13, 14, 15, 17, 28, 33, 34, 35, 36, 37, 40, 41, 42, 44, 45, 46, 47, 48, 49, 51, 52, 60, 64, 67, 68 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-05", "note": "" }, { "id": "CSC2", "text": "The Δ crossing rests on a randomized human perturbation with a positive registered primary endpoint in the scoped population: the 2026 pasteurized-Akkermansia weight-maintenance trial [53]. Obese-population strain/formulation trial signals and the randomized FMT fat-distribution contrast add supporting human evidence [9,21,23-25], but GutBugs was null on its BMI-SDS primary and on total body-fat percentage, so its prespecified secondary android/gynoid result, obtained without multiplicity control, supports rather than supplies the crossing. VSL3 high-energy-diet fat-gain attenuation [26] supports human physiology but is outside the registered obese-recipient gate. The 2026 pasteurized-Akk primary weight-maintenance benefit is additional clinical evidence [53], but does not alone establish a living-community or total-fat mechanism. Primary nulls, selected analyses, incomplete mediator attribution and access prevent Ε generalization [5,16,20,22,54-62,65-66]. No universal necessity or primacy burden is imposed on this contributory subclaim.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 3, 5, 8, 9, 11, 12, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 38, 39, 41, 43, 44, 50, 51, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 65, 66, 68 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-05", "note": "" }, { "id": "CSC3", "text": "Glucose/insulin and inflammatory effects do not by themselves establish body-fat control. Mouse depletion, human engraftment and clamp interventions can change those readouts without corresponding fat changes [11,14,18-19,38,40,43,52,54-59,63]. Positive fat trials retain their own credit in SC2; metabolic efficacy is not dismissed because complete mediation is absent.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 5, 9, 11, 14, 16, 18, 19, 20, 22, 23, 25, 26, 30, 33, 38, 40, 43, 52, 54, 55, 56, 57, 58, 61, 62, 63 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-05", "note": "" }, { "id": "CH", "text": "Microbes can causally alter adiposity in defined mice, and selected human interventions support a limited contribution to fat accumulation or weight maintenance. A general living microbial configuration that drives human obesity beyond diet and host physiology remains unestablished.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 2, 26, 9, 25, 53, 55, 62 ], "verification": "verified", "verified_against": "Bounded synthesis of examined sources; score is adjudication.", "verified_on": "2026-10-05", "note": "" } ], "citation_ledger": [ { "n": 1, "citation": "Turnbaugh PJ, Ley RE, Mahowald MA et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006.", "tier": "A", "kind": "primary", "pmid": "17183312", "doi": "10.1038/nature05414", "url": "https://pubmed.ncbi.nlm.nih.gov/17183312/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID17183312", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C1", "CSC1" ] }, { "n": 2, "citation": "Ridaura VK, Faith JJ, Rey FE et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science (New York, N.Y.). 2013.", "tier": "A", "kind": "primary", "pmid": "24009397", "doi": "10.1126/science.1241214", "url": "https://pubmed.ncbi.nlm.nih.gov/24009397/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID24009397", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C2", "CSC1", "CH" ] }, { "n": 3, "citation": "Goodrich JK, Waters JL, Poole AC et al. Human genetics shape the gut microbiome. Cell. 2014.", "tier": "A", "kind": "primary", "pmid": "25417156", "doi": "10.1016/j.cell.2014.09.053", "url": "https://pubmed.ncbi.nlm.nih.gov/25417156/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID25417156", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C3", "CSC1", "CSC2" ] }, { "n": 4, "citation": "Wang Y, Kuang Z, Yu X et al. The intestinal microbiota regulates body composition through NFIL3 and the circadian clock. Science (New York, N.Y.). 2017.", "tier": "A", "kind": "primary", "pmid": "28860383", "doi": "10.1126/science.aan0677", "url": "https://pubmed.ncbi.nlm.nih.gov/28860383/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID28860383", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C4", "CSC1" ] }, { "n": 5, "citation": "Zhang Y, Liu R, Chen Y et al. Akkermansia muciniphila supplementation in patients with overweight/obese type 2 diabetes: Efficacy depends on its baseline levels in the gut. Cell metabolism. 2025.", "tier": "A", "kind": "rct", "pmid": "39879980", "doi": "10.1016/j.cmet.2024.12.010", "url": "https://pubmed.ncbi.nlm.nih.gov/39879980/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "Live-Akk-NCT04797442", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C5", "CSC2", "CSC3" ] }, { "n": 6, "citation": "Bäckhed F, Ding H, Wang T et al. The gut microbiota as an environmental factor that regulates fat storage. Proceedings of the National Academy of Sciences of the United States of America. 2004.", "tier": "A", "kind": "primary", "pmid": "15505215", "doi": "10.1073/pnas.0407076101", "url": "https://pubmed.ncbi.nlm.nih.gov/15505215/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID15505215", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C6", "CSC1" ] }, { "n": 7, "citation": "Chassaing B, Koren O, Goodrich JK et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015.", "tier": "A", "kind": "primary", "pmid": "25731162", "doi": "10.1038/nature14232", "url": "https://pubmed.ncbi.nlm.nih.gov/25731162/", "status_flags": [ "ErratumIn: PMID27144359" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID25731162", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C7", "CSC1" ] }, { "n": 8, "citation": "Turnbaugh PJ, Hamady M, Yatsunenko T et al. A core gut microbiome in obese and lean twins. Nature. 2009.", "tier": "A", "kind": "primary", "pmid": "19043404", "doi": "10.1038/nature07540", "url": "https://pubmed.ncbi.nlm.nih.gov/19043404/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID19043404", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C8", "CSC2" ] }, { "n": 9, "citation": "Leong KSW, Jayasinghe TN, Wilson BC et al. Effects of Fecal Microbiome Transfer in Adolescents With Obesity: The Gut Bugs Randomized Controlled Trial. JAMA network open. 2020.", "tier": "A", "kind": "rct", "pmid": "33346848", "doi": "10.1001/jamanetworkopen.2020.30415", "url": "https://pubmed.ncbi.nlm.nih.gov/33346848/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "GutBugs-ACTRN12615001351505", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph1, 1:Methods:paragraph5, 1:Methods:paragraph6, 1:Methods:paragraph7, 1:Methods:paragraph9, 1:Methods:paragraph10, 2:Results:paragraph0, 2:Results:paragraph4, 2:Results:paragraph5, 2:Results:paragraph8. No complete-paper or supplement audit claimed.", "carries_claims": [ "C9", "CSC2", "CSC3", "CH" ] }, { "n": 10, "citation": "Kuang Z, Wang Y, Li Y et al. The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3. Science (New York, N.Y.). 2019.", "tier": "A", "kind": "primary", "pmid": "31604271", "doi": "10.1126/science.aaw3134", "url": "https://pubmed.ncbi.nlm.nih.gov/31604271/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-05", "status_checked_on": "2026-10-05", "study_id": "PMID31604271", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C10", "CSC1" ] }, { "n": 11, "citation": "Vrieze A, Van Nood E, Holleman F et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. 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No complete-paper or supplement audit claimed.", "carries_claims": [ "C68", "CSC1", "CSC2" ] } ], "independence_basis": { "required": true, "lines": [ { "label": "Recipient transfer and ecological rescue", "sources": [ 2, 3 ], "excludes_error": "Common recipient environments and lean/defined-strain amendment weaken donor-human lifestyle confounding; diet and cage invasion are explicit rather than assumed absent." }, { "label": "Defined microbial functions and host pathway instruments", "sources": [ 28, 12, 67, 37 ], "excludes_error": "Heterologous microbial gene, purified lipid, receptor/acetate rescue and defined-consortium pathway tests address different community-attribution errors; host background, lifelong manipulation and facility limits remain." }, { "label": "Controlled human adiposity and weight outcomes", "sources": [ 26, 9, 53, 55, 62 ], "excludes_error": "Randomized clinical exposure supplies human causal information while matched diet, engraftment-null and larger trial-null contrasts constrain generalization; distinct endpoints do not prove one identical pathway." } ], "shared_failure_mode_checked": true, "note": "SC1Ζ rests on multiple experimental error exclusions rather than article counts: transfer controls human-donor confounding, defined amendment narrows identity, and gene/receptor/metabolite rescue narrows function. Different pathways converge on modifiable recipient adiposity, not one universal strain. Human contribution is graded separately atΔ. GutBugs2020/2025, Mocanu2021/2024, Rinott2020online/2021issue plus2023secondary and preliminary2017/later2019Akk volunteers are report families. FMT studies have separate registrations; overlap elsewhere is unresolved rather than declared absent." }, "consensus_validation": { "completed": true, "status": "documented_historical_discovery_and_reconciliation", "provider": "Consensus", "provider_mode": "Historical browser/connector use as recorded in the source artifacts", "local_audit_date": "2026-10-09", "primary_comparison_count": null, "reported_usage": [], "grade_changed": false, "score_before": { "hsef_level": "Δ", "hsef_descriptor": "First field-valid causal perturbation crossed", "confidence": "Moderate", "confidence_rationale": "68 primary reports with 10 selected partial-body examinations; density, heterogeneous controls and incomplete access set the confidence, not correctness.", "rests_on_non_peer_reviewed_work": false, "rationale": "The preregistered scope-matched human-contribution gate SC2 yields Δ / Moderate. Selected controlled human adiposity contrasts cross the in-vivo causal boundary, so a blanket Γ on mouse-to-human inference is not reapplied to the convergent human set. SC1 reaches scoped Ζ for animal transmissibility/rescue; SC3 remains Γ for the endpoint-substitution inference. Weakest-link sensitivity is Γ, primary-subclaim and scope-matched Δ. A stronger universal or primary human-driver reading would remain Γ; that is a separate burden, not a requirement silently added to the registered contribution gate." }, "score_after": { "hsef_level": "Δ", "hsef_descriptor": "First field-valid causal perturbation crossed", "confidence": "Moderate", "confidence_rationale": "68 primary reports with 10 selected partial-body examinations; density, heterogeneous controls and incomplete access set the confidence, not correctness.", "rests_on_non_peer_reviewed_work": false, "rationale": "The preregistered scope-matched human-contribution gate SC2 yields Δ / Moderate. Selected controlled human adiposity contrasts cross the in-vivo causal boundary, so a blanket Γ on mouse-to-human inference is not reapplied to the convergent human set. SC1 reaches scoped Ζ for animal transmissibility/rescue; SC3 remains Γ for the endpoint-substitution inference. Weakest-link sensitivity is Γ, primary-subclaim and scope-matched Δ. A stronger universal or primary human-driver reading would remain Γ; that is a separate burden, not a requirement silently added to the registered contribution gate." }, "independent_blinded_audit": false, "raw_receipts": [ { "path": "deliverables\\hsef_v53_popularity_ranks_06_10_2026-10-05\\microbiome-human-obesity\\consensus\\consensus-result.png", "sha256": "327387cc43b420c97816028945d105e5430c9196f5d71bdfb144592cb2f9e18f" }, { "path": "deliverables\\hsef_v53_popularity_ranks_06_10_2026-10-05\\microbiome-human-obesity\\consensus\\deep-dom.txt", "sha256": "48268090776155eded861cd741b0935d99159f734f0c634cb298de7a52c6289c" }, { "path": "deliverables\\hsef_v53_popularity_ranks_06_10_2026-10-05\\microbiome-human-obesity\\consensus\\deep-response.txt", "sha256": "ec441ab26640132b8303f9cae4f52c2acbee36be972babfdcd590849c3957144" }, { "path": "deliverables\\hsef_v53_popularity_ranks_06_10_2026-10-05\\microbiome-human-obesity\\consensus\\final-dom.txt", "sha256": "4c7a94758721e91522f8c2a6150faddbbe3961497df8a8dfb7d02f21ba294635" }, { "path": "deliverables\\hsef_v53_popularity_ranks_06_10_2026-10-05\\microbiome-human-obesity\\consensus\\fulltext-check-response.txt", "sha256": "99c723c35ba0035430598c82730870fd7a0a3b0618021434242769fc913f0c99" } ], "limitations": "This verifies documented historical use and links the record to the final edition. 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