{ "$schema_version": "5.3", "review_mode": "fresh", "claim_restatement": { "index_wording": "Pasteurized Akkermansia muciniphila MucT supplementation improves clinically meaningful metabolic health in overweight insulin-resistant adults.", "entry_form": "claim", "gradeable_restatement": "Pasteurized Akkermansia muciniphila MucT supplementation causes clinically meaningful metabolic improvement under the registered glycemic/function criteria in overweight insulin-resistant adults.", "restatement_required": true, "split_into": [], "parent_claim": null, "scope_qualifiers": [ { "qualifier": "Baseline BMI, insulin resistance, diabetes status, age, product strain/preparation, dose, concurrent diet/drugs and follow-up; SC5 lead-in loss is antecedent to assessed regain, not retrospective responder exclusion.", "determinable_before_outcome": true, "determined_from": "Enrollment and experimental design, before results; no responder-defined scope.", "action": "retained" } ], "original_claim": "Pasteurized Akkermansia muciniphila MucT supplementation improves clinically meaningful metabolic health in overweight insulin-resistant adults.", "restatement_note": "The original broad metabolic-health wording is evaluated using its preregistered SC2 clinical glycemia/function gate, which excludes insulin-sensitivity markers alone. A newly discovered positive weight-maintenance proposition is scored separately as supplemental SC5, explicitly added after discovery and not the preregistered primary. This clarification does not turn a glycemic evidence gap into a claim that all metabolic benefits are absent." }, "hypothesis": { "name": "Pasteurized Akkermansia and Metabolic Health", "central_claim": "Pasteurized Akkermansia muciniphila MucT supplementation causes clinically meaningful metabolic improvement under the registered glycemic/function criteria in overweight insulin-resistant adults.", "proposed_mechanism": "Pasteurized Akkermansia muciniphila MucT supplementation improves clinically meaningful metabolic health in overweight insulin-resistant adults.", "claimed_scope": "Specified pasteurized MucT in adults overweight and insulin-resistant at enrollment, against placebo for clinical glycemic control or functional outcomes over at least 12 weeks. A separately declared post-discovery SC5 concerns 24-week weight maintenance after a pre-maintenance diet lead-in.", "claimed_level": [ "response", "maintenance" ], "is_conjunctive": false, "conjunctive_note": "The precise lead clinical proposition is SC2. Mechanism, competing-cause, generalization and safety companions remain separately reported; they do not replace the primary clinical endpoint." }, "rubric_routing": { "primary_rubric": "04-microbiome-systemic.md", "secondary_rubrics": [ "06-metabolism-aging.md" ], "index_notes_applied": [ "The precise lead clinical proposition is SC2. Mechanism, competing-cause, generalization and safety companions remain separately reported; they do not replace the primary clinical endpoint." ], "rubric_fit_note": "Rubric 04 fits microbial and factor hypotheses, with rubric 06 governing the clinical metabolic proxy-versus-phenotype boundary. A randomized specified-product intervention changing an objective clinical phenotype is a human sufficiency perturbation; it need not prove the organism is an endogenous disease cause. Pasteurized nonliving cells are not a colonization or endogenous propagation experiment. Literal transfer/rescue requirements are quoted with the explicit product-intervention adaptation; forced recipient transfer remains bounded to its actual experimental system. Lifespan is not imposed on the non-lifespan treatment claim." }, "subclaim_matrix": { "subclaims": [ { "id": "SC1", "statement": "The specified product changes host metabolic and barrier-related measures.", "subclaim_type": "mechanism", "scope": "MucT pasteurized preparation; overweight insulin-resistant adults without response-defined inclusion", "claimed_scope": "MucT pasteurized preparation; overweight insulin-resistant adults without response-defined inclusion", "governing_rubric": "04-microbiome-systemic.md", "key_evidence_anchor": "Controlled product and host assays", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "The specified preparation changes selected insulin, lipid and barrier-associated measures in the small 2019 trial, supported by experimental factor/barrier work. The 142-person trial has a null full-population primary Matsuda endpoint with exploratory subgroup marker changes. These observations show target-related physiological action, not a necessary isolated mediator or clinical phenotype crossing; the biomarker inference retains Γ.", "rubric_adaptation": "Controlled product/host readouts establish physiological action, but insulin indices, lipids, GLP1 and LPS are not clinical glycemic/function outcomes or mediator necessity." }, { "id": "SC2", "statement": "The product improves clinically meaningful metabolic health against placebo.", "subclaim_type": "sufficiency", "scope": "Baseline overweight and insulin resistance; clinical glycemic control or function over at least 12 weeks", "claimed_scope": "Baseline overweight and insulin resistance; clinical glycemic control or function over at least 12 weeks", "governing_rubric": "06-metabolism-aging.md", "key_evidence_anchor": "Human randomized clinical phenotype comparisons", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "The examined 2019 original body explicitly reports unchanged fasting glycemia and HbA1c, alongside improved HOMA/insulin markers. The larger MucT trial reports a null primary insulin-sensitivity endpoint and exploratory marker changes, not a verified full-scope clinically meaningful glycemic/function result. Other live strains, HB05 function and WBF mixtures cannot replace the registered product/population. Genuine 2026 MucT weight-maintenance benefit is separately retained in supplemental SC5.", "rubric_adaptation": "Assess the registered strain/preparation, overweight insulin-resistant population, at least 12-week duration and clinical glycemic/function endpoint; do not substitute another strain or the separately added weight-regain outcome." }, { "id": "SC3", "statement": "Benefits generalize across live strains, formulations and baseline metabolic disease.", "subclaim_type": "generalization", "scope": "Live versus pasteurized, strain and dose defined before outcome", "claimed_scope": "Live versus pasteurized, strain and dose defined before outcome", "governing_rubric": "04-microbiome-systemic.md", "key_evidence_anchor": "Direct strain and formulation comparisons", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Animal comparisons establish real strain/preparation effects, but directions differ: the one heat-killed preparation tested in 2013 failed, while later non-viable preparations improved selected measures (heat-killed EB-AMDK19 in beagles [7], heat-killed cells in STZ mice [44], and pasteurized preparations), and another species favors live treatment. The live AKK-WST01 human trial has no whole-group HbA1c/weight advantage, with low-baseline exploratory benefit. The HB05 older-adult functional and yogurt studies are genuine different-context results. These do not establish unrestricted clinical transfer across strains, preparations and baseline diseases.", "rubric_adaptation": "Require direct strain/preparation clinical comparisons and baseline-defined generalization. Mouse transfer/addition crosses only its experimental context and does not establish endogenous human necessity." }, { "id": "SC4", "statement": "Akkermansia abundance or generic probiotic effects establish efficacy of named commercial products.", "subclaim_type": "generalization", "scope": "Product identity and fiber context specified", "claimed_scope": "Product identity and fiber context specified", "governing_rubric": "04-microbiome-systemic.md", "key_evidence_anchor": "Direct product-specific trials rather than abundance correlation", "hsef_level": "Α", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Endogenous abundance correlations or an unrelated probiotic effect cannot establish efficacy of an identified commercial formulation. Some directly tested products, including WBF-011, have genuine specific clinical signals, but that is product-specific evidence rather than the proposed generic-to-named inference. This unsupported broad inference is speculative and does not mean every named product is ineffective.", "rubric_adaptation": "Require identifiable product-specific original trials, not a taxon signature or another formula; genuine trialed-product positives remain separate from generic inference." }, { "id": "SC5", "statement": "Pasteurized MucT reduces weight regain during a 24-week maintenance period after a diet lead-in.", "subclaim_type": "sufficiency", "scope": "Overweight/obese adults meeting pre-maintenance diet lead-in weight-loss criteria; baseline state known before assessed regain", "claimed_scope": "Overweight/obese adults meeting pre-maintenance diet lead-in weight-loss criteria; baseline state known before assessed regain", "governing_rubric": "06-metabolism-aging.md", "key_evidence_anchor": "The product-specific randomized maintenance trial", "hsef_level": "Δ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "The newly examined 90-person randomized trial reports lower 24-week regain with pasteurized MucT than placebo after a diet lead-in. This positive objective clinical phenotype crosses the first human sufficiency threshold for its prespecified maintenance setting. It was not our preregistered primary, does not establish glycemic efficacy in all insulin-resistant adults, and has not yet established generalization or independently replicated maintenance efficacy.", "rubric_adaptation": "A matched randomized 24-week product/placebo contrast on objective regain after a pre-maintenance lead-in is a clinical sufficiency perturbation. This supplemental claim is openly post-discovery and does not gate or retrospectively redefine SC2.", "preregistered": false, "added_after_source_discovery": true, "added_utc": "2026-10-13T16:18:20.009325+00:00", "primary_aggregation_gating": false } ], "aggregation_rule": "primary-subclaim", "aggregation_preregistered": true, "aggregation_rationale": "The precise lead clinical proposition is SC2. Mechanism, competing-cause, generalization and safety companions remain separately reported; they do not replace the primary clinical endpoint.", "primary_subclaim_id": "SC2", "aggregation_derivation": "The original preregistered primary SC2 returns Γ, with Moderate appraisal confidence, because target/insulin-sensitivity effects do not establish the registered clinical glycemia/function benefit. The positive 2026 randomized weight-maintenance finding is separately scored Δ in supplemental SC5. No positive trial is discarded, and no generic class or all-metabolic-benefits negative conclusion is inferred.", "aggregation_alternatives": { "weakest_link_would_return": "Α", "primary_subclaim_would_return": "Γ", "scope_matched_would_return": "Γ", "note": "Separate narrow successes do not replace the preregistered full-scope gate." }, "index_rule_deviation": "" }, "competing_models": { "models_evaluated": [ { "rank_in_tournament": 2, "model_id": "M1", "is_nominal": true, "name": "Product-specific clinical glycemic benefit", "core_claim": "Pasteurized MucT improves clinically meaningful glycemic/function outcomes in the registered population.", "explains_what_nominal_does_not": "Pasteurized MucT improves clinically meaningful glycemic/function outcomes in the registered population.", "strongest_supporting_evidence": [ "Controlled target-marker effects and strain/factor experiments provide partial support." ], "strongest_contradictory_evidence": [ "Clinical glycemia is null in the pilot body; the larger trial has a null insulin-sensitivity primary and exploratory subgroup signals." ], "hsef_level_for_this_model": "Γ", "rationale": "Controlled target-marker effects and strain/factor experiments provide partial support. Clinical glycemia is null in the pilot body; the larger trial has a null insulin-sensitivity primary and exploratory subgroup signals." }, { "rank_in_tournament": 1, "model_id": "M2", "is_nominal": false, "name": "Specific host signaling with incomplete clinical translation", "core_claim": "Microbial cell factors change barrier, insulin and lipid signaling without establishing every downstream clinical phenotype.", "explains_what_nominal_does_not": "Microbial cell factors change barrier, insulin and lipid signaling without establishing every downstream clinical phenotype.", "strongest_supporting_evidence": [ "Amuc_1100/P9 and other factor experiments plus the human marker-versus-glycemia dissociation fit this bounded mechanism." ], "strongest_contradictory_evidence": [ "Necessary human factor mediation is unresolved; the positive weight-regain trial shows some clinical translation is possible." ], "hsef_level_for_this_model": "Γ", "rationale": "Amuc_1100/P9 and other factor experiments plus the human marker-versus-glycemia dissociation fit this bounded mechanism. Necessary human factor mediation is unresolved; the positive weight-regain trial shows some clinical translation is possible." }, { "rank_in_tournament": 3, "model_id": "M3", "is_nominal": false, "name": "Diet and baseline host/community state drive response", "core_claim": "Dietary intervention and baseline ecology change glycemic/weight outcomes and microbial abundance together.", "explains_what_nominal_does_not": "Dietary intervention and baseline ecology change glycemic/weight outcomes and microbial abundance together.", "strongest_supporting_evidence": [ "High-fiber/energy-restriction and Mediterranean interventions change clinical glycemia; baseline abundance associates with dietary response." ], "strongest_contradictory_evidence": [ "Diet does not explain away matched randomized product effects; taxon correlations do not isolate the dietary mediator." ], "hsef_level_for_this_model": "Δ", "rationale": "High-fiber/energy-restriction and Mediterranean interventions change clinical glycemia; baseline abundance associates with dietary response. Diet does not explain away matched randomized product effects; taxon correlations do not isolate the dietary mediator." }, { "rank_in_tournament": 4, "model_id": "M4", "is_nominal": false, "name": "Strain and processing alter functional factors", "core_claim": "Different strains and preparation preserve or remove different active cell/factor functions.", "explains_what_nominal_does_not": "Different strains and preparation preserve or remove different active cell/factor functions.", "strongest_supporting_evidence": [ "The one heat-killed preparation tested in 2013 failed, while later heat-killed (beagle [7], STZ mouse [44]) and pasteurized preparations improved selected measures; novel-species live preference and direct yogurt contrasts map functional differences." ], "strongest_contradictory_evidence": [ "Animal processing differences are not universal human interchangeability rules and complete factor identity remains unresolved." ], "hsef_level_for_this_model": "Γ", "rationale": "The one heat-killed preparation tested in 2013 failed, while later heat-killed (beagle [7], STZ mouse [44]) and pasteurized preparations improved selected measures; novel-species live preference and direct yogurt contrasts map functional differences. Animal processing differences are not universal human interchangeability rules and complete factor identity remains unresolved." } ], "tournament_summary": "Descriptive comparison; does not modify the nominal score. The 2019 original PMID31263284 directly separates insulin/HOMA marker changes from unchanged fasting glycemia/HbA1c. The new product-specific weight-maintenance trial PMID42120725 provides a separate true clinical positive; it prevents interpreting incomplete glycemic translation as absence of all product benefit. Ranks measure how well each model accounts for the evidence bearing on the registered claim, not each model's own HSEF level; rank 3 carries Δ for its own dietary scope while ranking below two Γ models on the registered claim.", "study_separating_rank1_from_rank2": "The 2019 original PMID31263284 directly separates insulin/HOMA marker changes from unchanged fasting glycemia/HbA1c. The new product-specific weight-maintenance trial PMID42120725 provides a separate true clinical positive; it prevents interpreting incomplete glycemic translation as absence of all product benefit.", "nominal_wins_only_by_funding_artifact": false, "level_unchanged_by_tournament": true }, "evidence_inventory": [ { "n": 1, "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": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MUCT-NCT02637115", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 0:Online Methods:paragraph0, 0:Online Methods:paragraph1, 0:Online Methods:paragraph2, 0:Online Methods:paragraph3, 0:Online Methods:paragraph7, 0:Online Methods:paragraph8, 7:Main text (unsectioned body paragraphs):paragraph3, 7:Main text (unsectioned body paragraphs):paragraph4, 7:Main text (unsectioned body paragraphs):paragraph5, 7:Main text (unsectioned body paragraphs):paragraph9, 7:Main text (unsectioned body paragraphs):paragraph13, 7:Main text (unsectioned body paragraphs):paragraph14. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "The 40-enrolled/32-completed pilot found pasteurized Akkermansia improved insulin-sensitivity, insulin and cholesterol measures over three months; weight and fat differences were nonsignificant.", "what_it_does_not_show": "Small exploratory biomarker effects do not establish clinical glycemic control/function; live/pasteurized arms and parent-trial secondary reports require shared-study grouping.", "confounders_present": [ "Small exploratory biomarker effects do not establish clinical glycemic control/function; live/pasteurized arms and parent-trial secondary reports require shared-study grouping." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 2, "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": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MUCT-NCT05417360", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3", "SC5" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Ninety randomized adults undergoing an eight-week diet followed by 24-week maintenance regained less weight with pasteurized MucT than placebo, 1.2 versus 3.2 kg.", "what_it_does_not_show": "Genuine weight-maintenance benefit is not erased; baseline insulin-resistance eligibility and registered clinical glycemia/function endpoint require separate scope assessment, and active components were not isolated.", "confounders_present": [ "Genuine weight-maintenance benefit is not erased; baseline insulin-resistance eligibility and registered clinical glycemia/function endpoint require separate scope assessment, and active components were not isolated." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 3, "pmid": "39683431", "title": "Pasteurized Akkermansia muciniphila HB05 (HB05P) Improves Muscle Strength and Function: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.", "citation": "Kang CH, Jung ES, Jung SJ et al. Pasteurized Akkermansia muciniphila HB05 (HB05P) Improves Muscle Strength and Function: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients. 2024.", "doi": "10.3390/nu16234037", "pmcid": "PMC11643799", "url": "https://pubmed.ncbi.nlm.nih.gov/39683431/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39683431/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID39683431", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:2. Materials and Methods:paragraph1, 1:2. Materials and Methods:paragraph2, 1:2. Materials and Methods:paragraph3, 1:2. Materials and Methods:paragraph5, 2:3. Results:paragraph0, 2:3. Results:paragraph2, 2:3. Results:paragraph3, 2:3. Results:paragraph4, 2:3. Results:paragraph5. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "A 100-person 12-week older-adult HB05 trial reported improved left-leg extensor torque and follistatin compared with placebo.", "what_it_does_not_show": "Different strain and older functional population cannot establish MucT metabolic efficacy or all-strain generalization; a measured growth mediator is not necessity.", "confounders_present": [ "Different strain and older functional population cannot establish MucT metabolic efficacy or all-strain generalization; a measured growth mediator is not 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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 4, "pmid": "42343233", "title": "Effect of pasteurized Akkermansia muciniphila MucT on insulin sensitivity, body composition, and GLP-1 production in subjects with metabolic syndrome: impact of low baseline gut Akkermansia levels.", "citation": "Suenaert P, Segers A, Rymenans L et al. Effect of pasteurized Akkermansia muciniphila MucT on insulin sensitivity, body composition, and GLP-1 production in subjects with metabolic syndrome: impact of low baseline gut Akkermansia levels. Gut microbes. 2026.", "doi": "10.1080/19490976.2026.2690689", "pmcid": "PMC13313273", "url": "https://pubmed.ncbi.nlm.nih.gov/42343233/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/42343233/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MUCT-NCT05114018", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "A 142-person four-month MucT multicenter trial had a null primary Matsuda endpoint; subsequent exploratory baseline-low Akkermansia analyses found selected marker benefits.", "what_it_does_not_show": "Do not replace full-population null with an unconfirmed subgroup; GLP1/insulin-sensitivity proxies and weight P=.06 do not establish registered clinical glycemia/function benefit.", "confounders_present": [ "Do not replace full-population null with an unconfirmed subgroup; GLP1/insulin-sensitivity proxies and weight P=.06 do not establish registered clinical glycemia/function benefit." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 5, "pmid": "33477821", "title": "Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists.", "citation": "Depommier C, Vitale RM, Iannotti FA et al. Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists. Cells. 2021.", "doi": "10.3390/cells10010185", "pmcid": "PMC7832901", "url": "https://pubmed.ncbi.nlm.nih.gov/33477821/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33477821/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MUCT-NCT02637115", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Secondary analysis of the pilot found no global endocannabinoidome change, with selected mono-palmitoylglycerol changes and PPARalpha activity support.", "what_it_does_not_show": "Shares parent trial; univariate lipid differences and receptor activity do not isolate necessary human mediation or clinical benefit.", "confounders_present": [ "Shares parent trial; univariate lipid differences and receptor activity do not isolate necessary human mediation or clinical benefit." ], "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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [ "MUCT-NCT02637115" ] }, { "n": 6, "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": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID27892954", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "animal model", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Pasteurized bacteria and purified Amuc_1100 improved metabolic/barrier measures in obese/diabetic mice; the protein interacts with TLR2 and partially reproduces effects.", "what_it_does_not_show": "Mouse administration and a purified factor establish experimental sufficiency, not endogenous human necessity or clinically meaningful human outcomes.", "confounders_present": [ "Mouse administration and a purified factor establish experimental sufficiency, not endogenous human necessity or clinically meaningful human outcomes." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 7, "pmid": "39264284", "title": "Supplementation with heat-killed Akkermansia muciniphila EB-AMDK19 counteracts diet-induced overweight in beagles.", "citation": "Hong MG, Lee Y, Chung WS et al. Supplementation with heat-killed Akkermansia muciniphila EB-AMDK19 counteracts diet-induced overweight in beagles. Archives of animal nutrition. 2024.", "doi": "10.1080/1745039X.2024.2397221", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/39264284/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39264284/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID39264284", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Heat-killed EB-AMDK19 reduced diet-induced weight/fat/triglyceride gain in beagles over 12 weeks.", "what_it_does_not_show": "Different strain and canine prevention setting cannot establish human MucT clinical efficacy or universal pasteurized/live equivalence.", "confounders_present": [ "Different strain and canine prevention setting cannot establish human MucT clinical efficacy or universal pasteurized/live equivalence." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 8, "pmid": "41277957", "title": "Investigating the role of Akkermansia muciniphila Akk11 in modulating obesity and intestinal dysbiosis: a comparative study of live and pasteurized treatments.", "citation": "Feng S, Wang W, Zhang X et al. Investigating the role of Akkermansia muciniphila Akk11 in modulating obesity and intestinal dysbiosis: a comparative study of live and pasteurized treatments. Frontiers in microbiology. 2025.", "doi": "10.3389/fmicb.2025.1638771", "pmcid": "PMC12634622", "url": "https://pubmed.ncbi.nlm.nih.gov/41277957/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41277957/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41277957", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Live/pasteurized Akk11 improved adiposity and barrier measures in HFD mice with different microbial and fatty-acid responses.", "what_it_does_not_show": "Single-strain mouse exposure and differing fermentation responses do not establish formulation interchangeability in human clinical disease.", "confounders_present": [ "Single-strain mouse exposure and differing fermentation responses do not establish formulation interchangeability in human clinical disease." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 9, "pmid": "34683361", "title": "Effects of Live and Pasteurized Forms of Akkermansia from the Human Gut on Obesity and Metabolic Dysregulation.", "citation": "Choi Y, Bose S, Seo J et al. Effects of Live and Pasteurized Forms of Akkermansia from the Human Gut on Obesity and Metabolic Dysregulation. Microorganisms. 2021.", "doi": "10.3390/microorganisms9102039", "pmcid": "PMC8538271", "url": "https://pubmed.ncbi.nlm.nih.gov/34683361/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34683361/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID34683361", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Two strains in live/pasteurized form improved 12-week HFD mouse metabolic measures; pasteurized forms improved glucose tolerance more.", "what_it_does_not_show": "Mouse formulation comparison maps context, not human universal equivalence; administered microbes do not prove endogenous necessity.", "confounders_present": [ "Mouse formulation comparison maps context, not human universal equivalence; administered microbes do not prove endogenous 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 10, "pmid": "34863163", "title": "Extracellular vesicles and pasteurized cells derived from Akkermansia muciniphila protect against high-fat induced obesity in mice.", "citation": "Ashrafian F, Keshavarz Azizi Raftar S, Lari A et al. Extracellular vesicles and pasteurized cells derived from Akkermansia muciniphila protect against high-fat induced obesity in mice. Microbial cell factories. 2021.", "doi": "10.1186/s12934-021-01709-w", "pmcid": "PMC8645101", "url": "https://pubmed.ncbi.nlm.nih.gov/34863163/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34863163/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID34863163", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Live/pasteurized MucT and vesicles reduced HFD obesity/metabolic measures, with stronger selected effects for pasteurized cells and vesicles.", "what_it_does_not_show": "Food intake and broad microbiota changes are alternative mediators; vesicle/preventive mouse effects cannot establish human clinical control or factor necessity.", "confounders_present": [ "Food intake and broad microbiota changes are alternative mediators; vesicle/preventive mouse effects cannot establish human clinical control or factor 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 11, "pmid": "35805168", "title": "Identification and Characterization of a Novel Species of Genus Akkermansia with Metabolic Health Effects in a Diet-Induced Obesity Mouse Model.", "citation": "Kumar R, Kane H, Wang Q et al. Identification and Characterization of a Novel Species of Genus Akkermansia with Metabolic Health Effects in a Diet-Induced Obesity Mouse Model. Cells. 2022.", "doi": "10.3390/cells11132084", "pmcid": "PMC9265676", "url": "https://pubmed.ncbi.nlm.nih.gov/35805168/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35805168/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID35805168", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A novel Akkermansia species improved mouse weight/fat/insulin measures, with live form more effective than pasteurized.", "what_it_does_not_show": "Different species and opposite formulation preference limit universal pasteurization superiority; no direct human MucT endpoint.", "confounders_present": [ "Different species and opposite formulation preference limit universal pasteurization superiority; no direct human MucT 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 12, "pmid": "41568048", "title": "Probiotic attributes and safety profile of AKM Lab-01: a novel Akkermansia muciniphila strain combating obesity and metabolic disorders in diet-induced obese mice.", "citation": "Huang B, Xian Y, Xue W et al. Probiotic attributes and safety profile of AKM Lab-01: a novel Akkermansia muciniphila strain combating obesity and metabolic disorders in diet-induced obese mice. Frontiers in microbiology. 2025.", "doi": "10.3389/fmicb.2025.1627870", "pmcid": "PMC12815876", "url": "https://pubmed.ncbi.nlm.nih.gov/41568048/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41568048/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41568048", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "AKM Lab-01 live/processed preparations improved diet-induced mouse obesity/metabolic measures and had a mouse dietary safety study.", "what_it_does_not_show": "Calculated human safety extrapolation is not a human clinical trial or evidence of all-product long-term safety/equivalence.", "confounders_present": [ "Calculated human safety extrapolation is not a human clinical trial or evidence of all-product long-term safety/equivalence." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 13, "pmid": "35857132", "title": "Efficacy of multi-strain probiotic along with dietary and lifestyle modifications on polycystic ovary syndrome: a randomised, double-blind placebo-controlled study.", "citation": "Kaur I, Suri V, Sachdeva N et al. Efficacy of multi-strain probiotic along with dietary and lifestyle modifications on polycystic ovary syndrome: a randomised, double-blind placebo-controlled study. European journal of nutrition. 2022.", "doi": "10.1007/s00394-022-02959-z", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/35857132/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35857132/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID35857132", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "A six-month multi-strain plus fructooligosaccharide PCOS trial improved menstrual regularity, selected androgen/waist and quality-of-life outcomes with matched lifestyle advice.", "what_it_does_not_show": "Mixture-specific benefits do not establish MucT or every marketed probiotic; not all listed metabolic endpoints were positive.", "confounders_present": [ "Mixture-specific benefits do not establish MucT or every marketed probiotic; not all listed metabolic endpoints were positive." ], "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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 14, "pmid": "28935921", "title": "Probiotic reduces bacterial translocation in type 2 diabetes mellitus: A randomised controlled study.", "citation": "Sato J, Kanazawa A, Azuma K et al. Probiotic reduces bacterial translocation in type 2 diabetes mellitus: A randomised controlled study. Scientific reports. 2017.", "doi": "10.1038/s41598-017-12535-9", "pmcid": "PMC5608749", "url": "https://pubmed.ncbi.nlm.nih.gov/28935921/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28935921/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID28935921", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Lactobacillus casei Shirota fermented milk reduced measured bacterial translocation and changed fecal communities in 70 diabetic adults over 16 weeks.", "what_it_does_not_show": "No-probiotic control and translocation endpoint do not establish MucT clinical glycemic benefit; blood microbial assays require contamination care.", "confounders_present": [ "No-probiotic control and translocation endpoint do not establish MucT clinical glycemic benefit; blood microbial assays require contamination care." ], "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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 15, "pmid": "41097174", "title": "Bifidobacterium animalis subsp. lactis TISTR 2591 Improves Glycemic Control and Immune Response in Adults with Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Placebo-Controlled Crossover Clinical Trial.", "citation": "Khiaolaongam W, Boonyapranai K, Sitdhipol J et al. Bifidobacterium animalis subsp. lactis TISTR 2591 Improves Glycemic Control and Immune Response in Adults with Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Placebo-Controlled Crossover Clinical Trial. Nutrients. 2025.", "doi": "10.3390/nu17193097", "pmcid": "PMC12525656", "url": "https://pubmed.ncbi.nlm.nih.gov/41097174/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41097174/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41097174", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Six-week Bifidobacterium TISTR 2591 crossover attenuated a fasting-glucose rise and changed selected insulin/lipid measures, with no body-composition change.", "what_it_does_not_show": "Different strain, short duration and modest comparator deterioration cannot establish the 12-week MucT clinical claim or generic-product efficacy.", "confounders_present": [ "Different strain, short duration and modest comparator deterioration cannot establish the 12-week MucT clinical claim or generic-product 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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 16, "pmid": "41852479", "title": "Multi-strain probiotic reduces gastrointestinal side effects in women with elevated HOMA-IR index treated with metformin: a 12-week randomised controlled trial.", "citation": "Ratajczak M, Bilska A, Musialik K et al. Multi-strain probiotic reduces gastrointestinal side effects in women with elevated HOMA-IR index treated with metformin: a 12-week randomised controlled trial. Frontiers in endocrinology. 2026.", "doi": "10.3389/fendo.2026.1765741", "pmcid": "PMC12991998", "url": "https://pubmed.ncbi.nlm.nih.gov/41852479/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41852479/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41852479", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Twelve-week multi-strain supplementation alleviated metformin GI symptoms but did not add metabolic/anthropometric benefit in 30 insulin-resistant women.", "what_it_does_not_show": "Metformin-associated within-group improvements are not probiotic treatment effects; symptom benefit does not establish MucT clinical metabolism.", "confounders_present": [ "Metformin-associated within-group improvements are not probiotic treatment effects; symptom benefit does not establish MucT clinical metabolism." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 17, "pmid": "31090458", "title": "Three probiotic strains exert different effects on plasma bile acid profiles in healthy obese adults: randomised, double-blind placebo-controlled crossover study.", "citation": "Culpepper T, Rowe CC, Rusch CT et al. Three probiotic strains exert different effects on plasma bile acid profiles in healthy obese adults: randomised, double-blind placebo-controlled crossover study. Beneficial microbes. 2019.", "doi": "10.3920/BM2018.0151", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/31090458/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31090458/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID31090458", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Different probiotic strains altered selected plasma bile acids but not glucose, insulin or serum lipids in a placebo crossover study.", "what_it_does_not_show": "Biochemical target movement is not clinical efficacy and the strains are not MucT; washout/period and subset context remain relevant.", "confounders_present": [ "Biochemical target movement is not clinical efficacy and the strains are not MucT; washout/period and subset context remain relevant." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 18, "pmid": "34371847", "title": "Lactobacillus plantarum HAC01 Supplementation Improves Glycemic Control in Prediabetic Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial.", "citation": "Oh MR, Jang HY, Lee SY et al. Lactobacillus plantarum HAC01 Supplementation Improves Glycemic Control in Prediabetic Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2021.", "doi": "10.3390/nu13072337", "pmcid": "PMC8308899", "url": "https://pubmed.ncbi.nlm.nih.gov/34371847/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34371847/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID34371847", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Eight-week HAC01 trial in 40 prediabetic adults improved two-hour glucose/HbA1c versus placebo while several insulin/microbiota endpoints remained null.", "what_it_does_not_show": "A genuine different-strain clinical effect does not validate MucT or an unnamed commercial formula; duration is below its registered gate.", "confounders_present": [ "A genuine different-strain clinical effect does not validate MucT or an unnamed commercial formula; duration is below its registered gate." ], "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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 19, "pmid": "26084343", "title": "Intake of Lactobacillus reuteri improves incretin and insulin secretion in glucose-tolerant humans: a proof of concept.", "citation": "Simon MC, Strassburger K, Nowotny B et al. Intake of Lactobacillus reuteri improves incretin and insulin secretion in glucose-tolerant humans: a proof of concept. Diabetes care. 2015.", "doi": "10.2337/dc14-2690", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/26084343/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26084343/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID26084343", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Four-week L.reuteri in 21 glucose-tolerant adults increased incretin/insulin secretion without altering clamp insulin sensitivity, mass or ectopic fat.", "what_it_does_not_show": "Target engagement does not establish improved phenotype or MucT-specific mechanism; short and distinct exposure cannot support universal probiotics.", "confounders_present": [ "Target engagement does not establish improved phenotype or MucT-specific mechanism; short and distinct exposure cannot support universal probiotics." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 20, "pmid": "22695039", "title": "Probiotics to adolescents with obesity: effects on inflammation and metabolic syndrome.", "citation": "Gøbel RJ, Larsen N, Jakobsen M et al. Probiotics to adolescents with obesity: effects on inflammation and metabolic syndrome. Journal of pediatric gastroenterology and nutrition. 2012.", "doi": "10.1097/MPG.0b013e318263066c", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/22695039/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/22695039/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID22695039", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "Twelve-week L.salivarius Ls33 trial in 50 obese adolescents found no metabolic, inflammatory or anthropometric improvement versus placebo.", "what_it_does_not_show": "A product/context-specific null is a generalization boundary, not a refutation of MucT or every probiotic strain.", "confounders_present": [ "A product/context-specific null is a generalization boundary, not a refutation of MucT or every probiotic strain." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 21, "pmid": "37580231", "title": "No effect of multi-strain probiotic supplementation on metabolic and inflammatory markers and newborn body composition in pregnant women with obesity: Results from a randomized, double-blind placebo-controlled study.", "citation": "Halkjær SI, de Knegt VE, Kallemose T et al. No effect of multi-strain probiotic supplementation on metabolic and inflammatory markers and newborn body composition in pregnant women with obesity: Results from a randomized, double-blind placebo-controlled study. Nutrition, metabolism, and cardiovascular diseases : NMCD. 2023.", "doi": "10.1016/j.numecd.2023.07.030", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/37580231/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37580231/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID37580231", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "Multi-strain pregnancy trial found no metabolic/inflammatory or newborn-composition benefit despite high completion.", "what_it_does_not_show": "Pregnancy, mixture and developmental endpoints differ from MucT adult treatment; nulls cannot be erased by target presence.", "confounders_present": [ "Pregnancy, mixture and developmental endpoints differ from MucT adult treatment; nulls cannot be erased by target presence." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 22, "pmid": "36145254", "title": "The Roles of Probiotics in the Gut Microbiota Composition and Metabolic Outcomes in Asymptomatic Post-Gestational Diabetes Women: A Randomized Controlled Trial.", "citation": "Hasain Z, Raja Ali RA, Ahmad HF et al. The Roles of Probiotics in the Gut Microbiota Composition and Metabolic Outcomes in Asymptomatic Post-Gestational Diabetes Women: A Randomized Controlled Trial. Nutrients. 2022.", "doi": "10.3390/nu14183878", "pmcid": "PMC9504400", "url": "https://pubmed.ncbi.nlm.nih.gov/36145254/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36145254/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID36145254", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Twelve-week six-strain post-GDM trial reported modest fasting-glucose and HbA1c/lipid differences with microbiota shifts.", "what_it_does_not_show": "Mixture-specific biochemical/clinical glycemia effects cannot establish MucT identity or necessary microbiota mediation; long-term prevention was not demonstrated.", "confounders_present": [ "Mixture-specific biochemical/clinical glycemia effects cannot establish MucT identity or necessary microbiota mediation; long-term prevention was not demonstrated." ], "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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 23, "pmid": "26825666", "title": "Is there a value for probiotic supplements in gestational diabetes mellitus? A randomized clinical trial.", "citation": "Dolatkhah N, Hajifaraji M, Abbasalizadeh F et al. Is there a value for probiotic supplements in gestational diabetes mellitus? A randomized clinical trial. Journal of health, population, and nutrition. 2015.", "doi": "10.1186/s41043-015-0034-9", "pmcid": "PMC5026018", "url": "https://pubmed.ncbi.nlm.nih.gov/26825666/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26825666/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID26825666", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Eight-week four-strain GDM trial found greater fasting-glucose decline and late weight-gain differences, but adjusted sensitivity comparison was null.", "what_it_does_not_show": "Pregnancy-specific exposure and short horizon do not establish MucT or generic probiotics; within- versus between-group endpoints must remain separate.", "confounders_present": [ "Pregnancy-specific exposure and short horizon do not establish MucT or generic probiotics; within- versus between-group endpoints must remain separate." ], "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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 24, "pmid": "38953736", "title": "Beneficial effects of a new probiotic formulation on adipocytokines, appetite-regulating hormones, and metabolic parameters in obese women.", "citation": "Okuka N, Milinkovic N, Velickovic K et al. Beneficial effects of a new probiotic formulation on adipocytokines, appetite-regulating hormones, and metabolic parameters in obese women. Food & function. 2024.", "doi": "10.1039/d4fo01269k", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38953736/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38953736/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID38953736", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Two strains plus octacosanol altered CRP/ghrelin in obese women over 12 weeks but did not change BMI between groups.", "what_it_does_not_show": "Bundled active ingredient and marker-only changes cannot establish bacterial necessity, MucT clinical benefit or all-product efficacy.", "confounders_present": [ "Bundled active ingredient and marker-only changes cannot establish bacterial necessity, MucT clinical benefit or all-product 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 25, "pmid": "23899653", "title": "Effect of multispecies probiotic supplements on metabolic profiles, hs-CRP, and oxidative stress in patients with type 2 diabetes.", "citation": "Asemi Z, Zare Z, Shakeri H et al. Effect of multispecies probiotic supplements on metabolic profiles, hs-CRP, and oxidative stress in patients with type 2 diabetes. Annals of nutrition & metabolism. 2013.", "doi": "10.1159/000349922", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/23899653/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/23899653/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "ExpressionOfConcernIn: PMID37334997" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID23899653", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Eight-week multispecies trial reported attenuated fasting-glucose/HOMA rise and selected inflammatory/antioxidant changes.", "what_it_does_not_show": "Parent record has expression of concern PMID37334997; this flagged short mixture study is not used as decisive support or generalized to MucT.", "confounders_present": [ "Parent record has expression of concern PMID37334997; this flagged short mixture study is not used as decisive support or generalized to MucT." ], "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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 26, "pmid": "34229263", "title": "Supplementation with Bifidobacterium breve BR03 and B632 strains improved insulin sensitivity in children and adolescents with obesity in a cross-over, randomized double-blind placebo-controlled trial.", "citation": "Solito A, Bozzi Cionci N, Calgaro M et al. Supplementation with Bifidobacterium breve BR03 and B632 strains improved insulin sensitivity in children and adolescents with obesity in a cross-over, randomized double-blind placebo-controlled trial. Clinical nutrition (Edinburgh, Scotland). 2021.", "doi": "10.1016/j.clnu.2021.06.002", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/34229263/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34229263/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID34229263", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "B.breve crossover in obese youths found carryover requiring first-period analysis, with selected insulin-sensitivity changes but no cytokine/GLP1 shift.", "what_it_does_not_show": "Carryover and interval uncertainty constrain inference; childhood, strains and marker outcomes cannot establish MucT or universal efficacy.", "confounders_present": [ "Carryover and interval uncertainty constrain inference; childhood, strains and marker outcomes cannot establish MucT or universal 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 27, "pmid": "34956218", "title": "The Prebiotic Effects of Oats on Blood Lipids, Gut Microbiota, and Short-Chain Fatty Acids in Mildly Hypercholesterolemic Subjects Compared With Rice: A Randomized, Controlled Trial.", "citation": "Xu D, Feng M, Chu Y et al. The Prebiotic Effects of Oats on Blood Lipids, Gut Microbiota, and Short-Chain Fatty Acids in Mildly Hypercholesterolemic Subjects Compared With Rice: A Randomized, Controlled Trial. Frontiers in immunology. 2021.", "doi": "10.3389/fimmu.2021.787797", "pmcid": "PMC8697019", "url": "https://pubmed.ncbi.nlm.nih.gov/34956218/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34956218/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID34956218", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Oats versus rice in 210 adults reduced selected cholesterol fractions and increased Akkermansia/Roseburia abundance over 45 days.", "what_it_does_not_show": "Dietary components and correlated taxa do not isolate Akkermansia necessity or supplement-specific efficacy; both groups improved some lipids.", "confounders_present": [ "Dietary components and correlated taxa do not isolate Akkermansia necessity or supplement-specific efficacy; both groups improved some lipids." ], "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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 28, "pmid": "39710576", "title": "Multifunctional dietary approach reduces intestinal inflammation in relation with changes in gut microbiota composition in subjects at cardiometabolic risk: the SINFONI project.", "citation": "Hornero-Ramirez H, Morisette A, Marcotte B et al. Multifunctional dietary approach reduces intestinal inflammation in relation with changes in gut microbiota composition in subjects at cardiometabolic risk: the SINFONI project. Gut microbes. 2025.", "doi": "10.1080/19490976.2024.2438823", "pmcid": "PMC12931706", "url": "https://pubmed.ncbi.nlm.nih.gov/39710576/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39710576/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID39710576", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A 30-person multifunctional cereal crossover reduced local inflammation/endotoxemia and shifted microbiota, with unchanged cardiometabolic markers.", "what_it_does_not_show": "Multi-ingredient diet and marker movement cannot demonstrate a named probiotic clinical effect or bacterial mediation.", "confounders_present": [ "Multi-ingredient diet and marker movement cannot demonstrate a named probiotic clinical effect or bacterial 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 29, "pmid": "33096810", "title": "A High Protein Calorie Restriction Diet Alters the Gut Microbiome in Obesity.", "citation": "Dong TS, Luu K, Lagishetty V et al. A High Protein Calorie Restriction Diet Alters the Gut Microbiome in Obesity. Nutrients. 2020.", "doi": "10.3390/nu12103221", "pmcid": "PMC7590138", "url": "https://pubmed.ncbi.nlm.nih.gov/33096810/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33096810/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID33096810", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "High/normal-protein calorie restriction in 80 obese adults altered microbiota; both diets enriched Akkermansia and Bifidobacterium.", "what_it_does_not_show": "Diet-induced microbial abundance may accompany treatment response rather than cause it; no MucT product or necessity contrast.", "confounders_present": [ "Diet-induced microbial abundance may accompany treatment response rather than cause it; no MucT product or necessity contrast." ], "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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 30, "pmid": "42116498", "title": "Timing matters in type 2 diabetes: Early high-Fiber nutrition enhances glycemic control and reshapes gut microbiota.", "citation": "Wang L, Liang C, Yu J et al. Timing matters in type 2 diabetes: Early high-Fiber nutrition enhances glycemic control and reshapes gut microbiota. Food research international (Ottawa, Ont.). 2026.", "doi": "10.1016/j.foodres.2026.119257", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/42116498/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/42116498/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID42116498", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "A 34-person crossover of early high-fiber/energy-restricted nutrition improved clinical glycemia and shifted several taxa including Akkermansia.", "what_it_does_not_show": "Bundled energy restriction and sequence persistence preclude isolated fiber or taxon mediation; relative HbA1c-change percentages are not absolute percentage-point reductions.", "confounders_present": [ "Bundled energy restriction and sequence persistence preclude isolated fiber or taxon mediation; relative HbA1c-change percentages are not absolute percentage-point reductions." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 31, "pmid": "42158814", "title": "The Effects of a Prebiotic Formula Promoting Akkermansia muciniphila (AKK) on Gut Health: A Single-Centre, Randomised Controlled Trial.", "citation": "Wu CK, Cheng IS, Chung YC et al. The Effects of a Prebiotic Formula Promoting Akkermansia muciniphila (AKK) on Gut Health: A Single-Centre, Randomised Controlled Trial. International journal of medical sciences. 2026.", "doi": "10.7150/ijms.125881", "pmcid": "PMC13181376", "url": "https://pubmed.ncbi.nlm.nih.gov/42158814/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/42158814/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID42158814", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Eight-week prebiotic blend increased relative Akkermansia abundance in a per-protocol subset, with a trend in GI comfort.", "what_it_does_not_show": "Seventy randomized but fifty per-protocol; abundance increase and trend do not establish clinical metabolic benefit or MucT supplement efficacy.", "confounders_present": [ "Seventy randomized but fifty per-protocol; abundance increase and trend do not establish clinical metabolic benefit or MucT supplement 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 32, "pmid": "37049425", "title": "Consumption of Solnul™ Resistant Potato Starch Produces a Prebiotic Effect in a Randomized, Placebo-Controlled Clinical Trial.", "citation": "Bush JR, Baisley J, Harding SV et al. Consumption of Solnul™ Resistant Potato Starch Produces a Prebiotic Effect in a Randomized, Placebo-Controlled Clinical Trial. Nutrients. 2023.", "doi": "10.3390/nu15071582", "pmcid": "PMC10097138", "url": "https://pubmed.ncbi.nlm.nih.gov/37049425/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37049425/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID37049425", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Four-week resistant potato starch improved bowel-pattern measures and increased relative Bifidobacterium/Akkermansia versus placebo.", "what_it_does_not_show": "Short prebiotic laxation/abundance effects are distinct from MucT clinical metabolism and do not isolate one taxon's necessity.", "confounders_present": [ "Short prebiotic laxation/abundance effects are distinct from MucT clinical metabolism and do not isolate one taxon's 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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 33, "pmid": "36841667", "title": "Associations of Dietary Intake with the Intestinal Microbiota and Short-Chain Fatty Acids Among Young Adults with Type 1 Diabetes and Overweight or Obesity.", "citation": "Igudesman D, Crandell JL, Corbin KD et al. Associations of Dietary Intake with the Intestinal Microbiota and Short-Chain Fatty Acids Among Young Adults with Type 1 Diabetes and Overweight or Obesity. The Journal of nutrition. 2023.", "doi": "10.1016/j.tjnut.2022.12.017", "pmcid": "PMC10356993", "url": "https://pubmed.ncbi.nlm.nih.gov/36841667/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36841667/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID36841667", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Dietary analyses within a weight-loss trial associated fiber with fecal acetate and fructose inversely with Akkermansia in young adults with T1D.", "what_it_does_not_show": "Nonrandomized diet/taxon associations and limited repeated sampling do not establish MucT efficacy or a universal fiber-to-Akkermansia pathway.", "confounders_present": [ "Nonrandomized diet/taxon associations and limited repeated sampling do not establish MucT efficacy or a universal fiber-to-Akkermansia pathway." ], "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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 34, "pmid": "41636295", "title": "Efficacy of inulin supplementation in metabolic control and Akkermansia muciniphila levels in subjects with type 1 diabetes: a pilot study.", "citation": "Ojetti V, Saviano A, Rizzi A et al. Efficacy of inulin supplementation in metabolic control and Akkermansia muciniphila levels in subjects with type 1 diabetes: a pilot study. European review for medical and pharmacological sciences. 2026.", "doi": "10.26355/eurrev_202601_37645", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/41636295/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41636295/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41636295", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Three-month inulin plus insulin in 49 T1D adults modestly reduced weight/insulin need but did not improve HbA1c/CGM or Akkermansia levels versus insulin alone.", "what_it_does_not_show": "A fiber clinical change can occur without increased Akkermansia; different diabetes and product context cannot establish pasteurized MucT efficacy.", "confounders_present": [ "A fiber clinical change can occur without increased Akkermansia; different diabetes and product context cannot establish pasteurized MucT 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 35, "pmid": "30420171", "title": "Fecal Akkermansia muciniphila Is Associated with Body Composition and Microbiota Diversity in Overweight and Obese Women with Breast Cancer Participating in a Presurgical Weight Loss Trial.", "citation": "Frugé AD, Van der Pol W, Rogers LQ et al. Fecal Akkermansia muciniphila Is Associated with Body Composition and Microbiota Diversity in Overweight and Obese Women with Breast Cancer Participating in a Presurgical Weight Loss Trial. Journal of the Academy of Nutrition and Dietetics. 2020.", "doi": "10.1016/j.jand.2018.08.164", "pmcid": "PMC6509025", "url": "https://pubmed.ncbi.nlm.nih.gov/30420171/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30420171/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "NCT02224807", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Pooled secondary breast-cancer weight-loss trial analysis associated baseline Akkermansia with adiposity and fiber change in low-abundance participants.", "what_it_does_not_show": "Randomized diet does not randomize bacterial abundance; small disease-selected associations cannot prove taxon mediation or named-product clinical efficacy.", "confounders_present": [ "Randomized diet does not randomize bacterial abundance; small disease-selected associations cannot prove taxon mediation or named-product clinical 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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 36, "pmid": "42489745", "title": "Distinct effects of supplementation with resistant starch and polydextrose on plasma and faecal bile acid profile and associations with gut microbiota: a randomised, controlled intervention in healthy participants.", "citation": "Fan J, le Gall G, Malcomson FC et al. Distinct effects of supplementation with resistant starch and polydextrose on plasma and faecal bile acid profile and associations with gut microbiota: a randomised, controlled intervention in healthy participants. European journal of nutrition. 2026.", "doi": "10.1007/s00394-026-04060-1", "pmcid": "PMC13396052", "url": "https://pubmed.ncbi.nlm.nih.gov/42489745/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/42489745/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "DISC-NCT01214681", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Resistant starch and polydextrose had distinct bile-acid effects, with fiber-specific Akkermansia correlations in the DISC trial.", "what_it_does_not_show": "Biochemical correlations are not necessary microbial mediation or clinical metabolic health; formulations cannot be grouped as uniform fiber effects.", "confounders_present": [ "Biochemical correlations are not necessary microbial mediation or clinical metabolic health; formulations cannot be grouped as uniform fiber effects." ], "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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 37, "pmid": "32698959", "title": "Acute and chronic improvement in postprandial glucose metabolism by a diet resembling the traditional Mediterranean dietary pattern: Can SCFAs play a role?", "citation": "Vitale M, Giacco R, Laiola M et al. Acute and chronic improvement in postprandial glucose metabolism by a diet resembling the traditional Mediterranean dietary pattern: Can SCFAs play a role? Clinical nutrition (Edinburgh, Scotland). 2021.", "doi": "10.1016/j.clnu.2020.05.025", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/32698959/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32698959/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID32698959", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "An isoenergetic Mediterranean-diet trial improved postprandial glucose responses with SCFA and Akkermansia shifts over eight weeks.", "what_it_does_not_show": "Whole-diet composition and short horizon cannot identify Akkermansia-specific causal contribution or validate a MucT product.", "confounders_present": [ "Whole-diet composition and short horizon cannot identify Akkermansia-specific causal contribution or validate a MucT product." ], "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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 38, "pmid": "30396006", "title": "Alterations in gut microbiota composition and metabolic parameters after dietary intervention with barley beta glucans in patients with high risk for metabolic syndrome development.", "citation": "Velikonja A, Lipoglavšek L, Zorec M et al. Alterations in gut microbiota composition and metabolic parameters after dietary intervention with barley beta glucans in patients with high risk for metabolic syndrome development. Anaerobe. 2019.", "doi": "10.1016/j.anaerobe.2018.11.002", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30396006/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30396006/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID30396006", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Four-week barley beta-glucan bread changed cholesterol/SCFA measures; baseline taxa differed in cholesterol responders.", "what_it_does_not_show": "Within-group cholesterol change and post-outcome responder classification cannot establish between-group clinical microbial causality or define an unfalsifiable subgroup.", "confounders_present": [ "Within-group cholesterol change and post-outcome responder classification cannot establish between-group clinical microbial causality or define an unfalsifiable subgroup." ], "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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 39, "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": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID23671105", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "animal model", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "Live Akkermansia reversed HFD metabolic abnormalities in mice, whereas the tested heat-killed preparation did not; prebiotic normalization correlated with improved measures.", "what_it_does_not_show": "Heat-killed and later pasteurized preparation protocols are not identical; experimental sufficiency does not prove endogenous human necessity or universal live superiority.", "confounders_present": [ "Heat-killed and later pasteurized preparation protocols are not identical; experimental sufficiency does not prove endogenous human necessity or universal live superiority." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 40, "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": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "WST01-NCT04797442", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "Twelve-week live AKK-WST01 trial in 58 overweight/obese T2D adults had no whole-group HbA1c or weight advantage; low-baseline exploratory participants showed selected benefit and colonization.", "what_it_does_not_show": "Different live strain and subgroup contrasts cannot establish broad pasteurized MucT efficacy; within-subgroup significance is not automatically an interaction or independent replicated subgroup.", "confounders_present": [ "Different live strain and subgroup contrasts cannot establish broad pasteurized MucT efficacy; within-subgroup significance is not automatically an interaction or independent replicated subgroup." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 41, "pmid": "33820962", "title": "Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice.", "citation": "Yoon HS, Cho CH, Yun MS et al. Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nature microbiology. 2021.", "doi": "10.1038/s41564-021-00880-5", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33820962/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33820962/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID33820962", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Purified P9 increased GLP1/thermogenesis in mice and cells; IL6 deficiency abolished selected glucose-homeostasis effects and altered its receptor pathway.", "what_it_does_not_show": "Factor sufficiency and a knockout narrow an experimental mechanism, but do not establish that P9 mediates human pasteurized MucT clinical outcomes.", "confounders_present": [ "Factor sufficiency and a knockout narrow an experimental mechanism, but do not establish that P9 mediates human pasteurized MucT clinical outcomes." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 42, "pmid": "26100928", "title": "Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology.", "citation": "Dao MC, Everard A, Aron-Wisnewsky J et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2016.", "doi": "10.1136/gutjnl-2014-308778", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/26100928/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26100928/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "DAO-NCT01314690", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "In a 49-person calorie-restriction/stabilization cohort, higher baseline Akkermansia associated with healthier status and better metabolic response while abundance subsequently declined.", "what_it_does_not_show": "Diet and bacterial abundance are not independently randomized; a decrease alongside improvement limits a simple more-is-better abundance interpretation.", "confounders_present": [ "Diet and bacterial abundance are not independently randomized; a decrease alongside improvement limits a simple more-is-better abundance interpretation." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 43, "pmid": "32675291", "title": "Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation.", "citation": "Perraudeau F, McMurdie P, Bullard J et al. Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ open diabetes research & care. 2020.", "doi": "10.1136/bmjdrc-2020-001319", "pmcid": "PMC7368581", "url": "https://pubmed.ncbi.nlm.nih.gov/32675291/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32675291/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "WBF-NCT03893422", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Twelve-week WBF-011 mixture trial in 76 T2D adults improved postprandial glucose primary outcome and reported lower HbA1c relative to placebo.", "what_it_does_not_show": "The five-strain/inulin product is genuinely trialed but cannot identify Akkermansia component necessity or validate MucT, another formula or every probiotic.", "confounders_present": [ "The five-strain/inulin product is genuinely trialed but cannot identify Akkermansia component necessity or validate MucT, another formula or every probiotic." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 44, "pmid": "39429872", "title": "Akkermansia muciniphila administration ameliorates streptozotocin-induced hyperglycemia and muscle atrophy by promoting IGF2 secretion from mouse intestine.", "citation": "Zhang C, Wang Z, Liu X et al. Akkermansia muciniphila administration ameliorates streptozotocin-induced hyperglycemia and muscle atrophy by promoting IGF2 secretion from mouse intestine. iMeta. 2024.", "doi": "10.1002/imt2.237", "pmcid": "PMC11487547", "url": "https://pubmed.ncbi.nlm.nih.gov/39429872/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39429872/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID39429872", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Heat-killed Akkermansia improved STZ-mouse metabolic/muscle signaling, with intestinal IGF2 secretion and downstream muscle effects.", "what_it_does_not_show": "Survival-selected STZ context and experimental heat-killed treatment are not a pasteurized MucT human functional trial or mediator necessity demonstration.", "confounders_present": [ "Survival-selected STZ context and experimental heat-killed treatment are not a pasteurized MucT human functional trial or mediator necessity demonstration." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 45, "pmid": "41273480", "title": "Akkermansia muciniphila alleviates metabolic disorders through gut microbiota-mediated tryptophan regulation.", "citation": "Zhang F, Tian J, Li JT et al. Akkermansia muciniphila alleviates metabolic disorders through gut microbiota-mediated tryptophan regulation. AMB Express. 2025.", "doi": "10.1186/s13568-025-01986-3", "pmcid": "PMC12748435", "url": "https://pubmed.ncbi.nlm.nih.gov/41273480/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41273480/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41273480", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Akkermansia improved HFD zebrafish weight/survival and barrier measures; antibiotic pretreatment partly abolished selected effects with tryptophan/AhR changes.", "what_it_does_not_show": "Broad antibiotics and metabolite associations do not isolate the exact human product or necessary human mediator; species and diet context remain explicit.", "confounders_present": [ "Broad antibiotics and metabolite associations do not isolate the exact human product or necessary human mediator; species and diet context remain explicit." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 46, "pmid": "42207914", "title": "Akkermansia muciniphila-derived L-norleucine modulates FABP1-dependent fatty acid transport.", "citation": "Li J, Ma Z, Zhang J et al. Akkermansia muciniphila-derived L-norleucine modulates FABP1-dependent fatty acid transport. Proceedings of the National Academy of Sciences of the United States of America. 2026.", "doi": "10.1073/pnas.2533286123", "pmcid": "PMC13229228", "url": "https://pubmed.ncbi.nlm.nih.gov/42207914/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/42207914/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID42207914", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Intestinal FABP1 knockout and microbiota depletion narrowed lipid-absorption biology; Akkermansia supplementation and L-norleucine inhibited selected obesity/fatty-acid outcomes.", "what_it_does_not_show": "A bacterial abundance/metabolite link and factor sufficiency do not establish human pasteurized MucT glycemic efficacy or endogenous bacterial necessity.", "confounders_present": [ "A bacterial abundance/metabolite link and factor sufficiency do not establish human pasteurized MucT glycemic efficacy or endogenous bacterial 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 47, "pmid": "39628971", "title": "Akkermansia muciniphila in patients with metabolic dysfunction-associated steatotic liver disease.", "citation": "Mihele AI, Lazar L. Akkermansia muciniphila in patients with metabolic dysfunction-associated steatotic liver disease. Journal of medicine and life. 2024.", "doi": "10.25122/jml-2024-0342", "pmcid": "PMC11611053", "url": "https://pubmed.ncbi.nlm.nih.gov/39628971/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39628971/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID39628971", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "MASLD cohort of 122 associated Akkermansia with GGT, HDL and glycemia but not ALT or AST.", "what_it_does_not_show": "Clinical/taxon correlations and speculative oxidative-stress interpretation cannot establish product efficacy or microbial mediation.", "confounders_present": [ "Clinical/taxon correlations and speculative oxidative-stress interpretation cannot establish product efficacy or 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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 48, "pmid": "41511159", "title": "Akkermansia muciniphila modulates intestinal mucus composition to counteract high-fat diet-induced obesity in mice.", "citation": "Paone P, Petitfils C, Puel A et al. Akkermansia muciniphila modulates intestinal mucus composition to counteract high-fat diet-induced obesity in mice. Gut microbes. 2026.", "doi": "10.1080/19490976.2025.2612580", "pmcid": "PMC12795273", "url": "https://pubmed.ncbi.nlm.nih.gov/41511159/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41511159/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41511159", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Six-week live MucT in HFD mice reduced adiposity and changed mucus glycans/barrier markers without changing overall microbiota or mucus thickness.", "what_it_does_not_show": "Living mouse supplement effects do not establish pasteurized human clinical efficacy; a mucus-composition association is not necessary mediator ablation.", "confounders_present": [ "Living mouse supplement effects do not establish pasteurized human clinical efficacy; a mucus-composition association is not necessary mediator ablation." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 49, "pmid": "29379988", "title": "Aberrant intestinal microbiota in individuals with prediabetes.", "citation": "Allin KH, Tremaroli V, Caesar R et al. Aberrant intestinal microbiota in individuals with prediabetes. Diabetologia. 2018.", "doi": "10.1007/s00125-018-4550-1", "pmcid": "PMC6448993", "url": "https://pubmed.ncbi.nlm.nih.gov/29379988/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29379988/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID29379988", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Prediabetes case-control microbiota had lower Akkermansia; fecal transfers from prediabetic/drug-naive diabetic donors did not impair recipient glucose regulation.", "what_it_does_not_show": "A whole-community transfer null does not refute all Akkermansia product effects, but association cannot be counted as transferable glucose disease.", "confounders_present": [ "A whole-community transfer null does not refute all Akkermansia product effects, but association cannot be counted as transferable glucose disease." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 50, "pmid": "40451504", "title": "Comparing the effects of yogurt containing Akkermansia muciniphilia postbiotic with yogurt containing Lactobacillus rhamnosus postbiotic on body composition, biochemical indices, appetite, and depression scores in overweight or obese adults: A randomized, double-blind, controlled clinical trial.", "citation": "Aalipanah E, Askarpour M, Eskandari MH et al. Comparing the effects of yogurt containing Akkermansia muciniphilia postbiotic with yogurt containing Lactobacillus rhamnosus postbiotic on body composition, biochemical indices, appetite, and depression scores in overweight or obese adults: A randomized, double-blind, controlled clinical trial. Clinical nutrition ESPEN. 2025.", "doi": "10.1016/j.clnesp.2025.05.045", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40451504/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40451504/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID40451504", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Eight-week Akkermansia-postbiotic yogurt in 66 randomized adults improved selected waist, fat, AST and appetite outcomes versus low-fat yogurt; L.rhamnosus yogurt did not.", "what_it_does_not_show": "Different formulation/strain details, multiple endpoints and short horizon cannot validate MucT's registered clinical glycemic/function claim; genuine context positives are retained.", "confounders_present": [ "Different formulation/strain details, multiple endpoints and short horizon cannot validate MucT's registered clinical glycemic/function claim; genuine context positives are retained." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 51, "pmid": "41112049", "title": "Akkermansia muciniphila-derived hypoacylated rough-type lipopolysaccharides alleviate diet-induced obesity via activation of TLR4-IL-23-IL-22 immune axis.", "citation": "Sun L, Zhang Y, Dong W et al. Akkermansia muciniphila-derived hypoacylated rough-type lipopolysaccharides alleviate diet-induced obesity via activation of TLR4-IL-23-IL-22 immune axis. iMeta. 2025.", "doi": "10.1002/imt2.70066", "pmcid": "PMC12527988", "url": "https://pubmed.ncbi.nlm.nih.gov/41112049/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41112049/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41112049", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Akkermansia-derived LPS improved obese-mouse measures; IL22 neutralization eliminated selected antiobesity effects with TLR4/IL23 pathway evidence.", "what_it_does_not_show": "Intraperitoneal purified LPS and acute mouse toxicity comparison are not oral MucT human efficacy or universal bacterial-LPS safety.", "confounders_present": [ "Intraperitoneal purified LPS and acute mouse toxicity comparison are not oral MucT human efficacy or universal bacterial-LPS safety." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 52, "pmid": "37866242", "title": "Akkermansia muciniphila and its outer membrane protein Amuc_1100 prevent high-fat diet-induced nonalcoholic fatty liver disease in mice.", "citation": "Qu D, Chen M, Zhu H et al. Akkermansia muciniphila and its outer membrane protein Amuc_1100 prevent high-fat diet-induced nonalcoholic fatty liver disease in mice. Biochemical and biophysical research communications. 2023.", "doi": "10.1016/j.bbrc.2023.149131", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/37866242/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37866242/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID37866242", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Akkermansia/Amuc_1100 reduced HFD mouse weight/liver injury and metabolic measures with atorvastatin as a positive comparator.", "what_it_does_not_show": "Broad gut/liver changes and factor administration do not establish human clinical glycemic/function effects or a unique necessary pathway.", "confounders_present": [ "Broad gut/liver changes and factor administration do not establish human clinical glycemic/function effects or a unique necessary pathway." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 53, "pmid": "29472701", "title": "Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions.", "citation": "Chelakkot C, Choi Y, Kim DK et al. Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions. Experimental & molecular medicine. 2018.", "doi": "10.1038/emm.2017.282", "pmcid": "PMC5903829", "url": "https://pubmed.ncbi.nlm.nih.gov/29472701/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29472701/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID29472701", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Akkermansia vesicles improved HFD mouse weight/glucose tolerance and cell barrier function; E.coli vesicles did not reproduce selected barrier effects.", "what_it_does_not_show": "Vesicle sufficiency and experimental positive/negative control do not establish intact pasteurized MucT clinical efficacy or vesicle necessity in humans.", "confounders_present": [ "Vesicle sufficiency and experimental positive/negative control do not establish intact pasteurized MucT clinical efficacy or vesicle necessity in humans." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 54, "pmid": "34030573", "title": "Gut Akkermansia muciniphila ameliorates metabolic dysfunction-associated fatty liver disease by regulating the metabolism of L-aspartate via gut-liver axis.", "citation": "Rao Y, Kuang Z, Li C et al. Gut Akkermansia muciniphila ameliorates metabolic dysfunction-associated fatty liver disease by regulating the metabolism of L-aspartate via gut-liver axis. Gut microbes. 2021.", "doi": "10.1080/19490976.2021.1927633", "pmcid": "PMC8158032", "url": "https://pubmed.ncbi.nlm.nih.gov/34030573/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34030573/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID34030573", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Akkermansia and L-aspartate improved HFC-mouse fatty-liver measures, with persistent effects after withdrawal and partial antibiotic attenuation.", "what_it_does_not_show": "Broad antibiotic, metabolite and liver-pathology contrasts do not isolate the human product or convert a model-specific liver result to clinical glycemic control.", "confounders_present": [ "Broad antibiotic, metabolite and liver-pathology contrasts do not isolate the human product or convert a model-specific liver result to clinical glycemic 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 55, "pmid": "40041901", "title": "Akkermansia muciniphila-derived acetate activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis in metabolic-associated fatty liver disease.", "citation": "Zhuge A, Li S, Han S et al. Akkermansia muciniphila-derived acetate activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis in metabolic-associated fatty liver disease. Acta pharmaceutica Sinica. B. 2025.", "doi": "10.1016/j.apsb.2024.10.010", "pmcid": "PMC11873632", "url": "https://pubmed.ncbi.nlm.nih.gov/40041901/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40041901/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID40041901", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Mouse/germ-free studies and AMPK deficiency support an Akkermansia-acetate pathway reducing selected hepatic ferroptotic injury measures.", "what_it_does_not_show": "AMPK dependence and colonization narrow animal factor biology; no human clinical MucT endpoint or mediator necessity is established.", "confounders_present": [ "AMPK dependence and colonization narrow animal factor biology; no human clinical MucT endpoint or mediator necessity is 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 56, "pmid": "33323004", "title": "From correlation to causality: the case of Subdoligranulum.", "citation": "Van Hul M, Le Roy T, Prifti E et al. From correlation to causality: the case of Subdoligranulum. Gut microbes. 2020.", "doi": "10.1080/19490976.2020.1849998", "pmcid": "PMC7744154", "url": "https://pubmed.ncbi.nlm.nih.gov/33323004/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33323004/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID33323004", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Subdoligranulum abundance associated with healthier human metabolic measures, but its cultured-strain supplementation did not improve eight-week obese/diabetic mouse outcomes.", "what_it_does_not_show": "A clear association-to-intervention boundary for another taxon cannot establish MucT inefficacy; it warns against generic abundance/product inference.", "confounders_present": [ "A clear association-to-intervention boundary for another taxon cannot establish MucT inefficacy; it warns against generic abundance/product 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 57, "pmid": "35812447", "title": "BATF3 Protects Against Metabolic Syndrome and Maintains Intestinal Epithelial Homeostasis.", "citation": "Hamade H, Stamps JT, Stamps DT et al. BATF3 Protects Against Metabolic Syndrome and Maintains Intestinal Epithelial Homeostasis. Frontiers in immunology. 2022.", "doi": "10.3389/fimmu.2022.841065", "pmcid": "PMC9257242", "url": "https://pubmed.ncbi.nlm.nih.gov/35812447/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35812447/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID35812447", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Batf3 deficiency altered barrier/immune/microbiota state and metabolic syndrome; antibiotic and glycolysis interventions changed selected outcomes.", "what_it_does_not_show": "Developmental host-gene perturbation and broad antibiotics cannot attribute syndrome specifically to Akkermansia or demonstrate human product efficacy.", "confounders_present": [ "Developmental host-gene perturbation and broad antibiotics cannot attribute syndrome specifically to Akkermansia or demonstrate human product 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 58, "pmid": "40795248", "title": "Mucin-dependent transcriptional dynamics of Akkermansia muciniphila in co-culture with human colonic organoids.", "citation": "Matsuzaki M, Imai A, Yanagisawa K et al. Mucin-dependent transcriptional dynamics of Akkermansia muciniphila in co-culture with human colonic organoids. Bioscience, biotechnology, and biochemistry. 2025.", "doi": "10.1093/bbb/zbaf121", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40795248/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40795248/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID40795248", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "in vitro", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Human colonic organoid co-culture with goblet-cell-deficient controls showed mucin-dependent Akkermansia transcription and host-interaction genes.", "what_it_does_not_show": "A model-specific microbial transcription response is not clinical metabolism or proof of pasteurized human-product mechanism.", "confounders_present": [ "A model-specific microbial transcription response is not clinical metabolism or proof of pasteurized human-product 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 59, "pmid": "38811534", "title": "Binding of Akkermansia muciniphila to mucin is O-glycan specific.", "citation": "Elzinga J, Narimatsu Y, de Haan N et al. Binding of Akkermansia muciniphila to mucin is O-glycan specific. Nature communications. 2024.", "doi": "10.1038/s41467-024-48770-8", "pmcid": "PMC11137150", "url": "https://pubmed.ncbi.nlm.nih.gov/38811534/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38811534/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID38811534", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "in vitro", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Cell-based mucin arrays identify O-glycan-specific Akkermansia binding retained after pasteurization, with neuraminidase revealing binding epitopes.", "what_it_does_not_show": "Adhesion survives processing but colonization/function and clinical glycemic benefit are not thereby established.", "confounders_present": [ "Adhesion survives processing but colonization/function and clinical glycemic benefit are not thereby 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] } ], "verification_summary": { "load_bearing_claims_checked": 65, "verified": 65, "unverified": 0, "contradicted": 0, "note": "Verified attribution is distinct from mechanism truth or complete body access." }, "factual_issues_found": [], "cap_rules_applied": [ { "subclaim_id": "SC1", "cap": "Γ", "cap_source": "universal", "triggered": true, "trigger_text_quoted": "Biomarker change without functional/phenotypic change caps at Γ.", "specific_trigger": "The specified preparation changes selected insulin, lipid and barrier-associated measures in the small 2019 trial, supported by experimental factor/barrier work. The 142-person trial has a null full-population primary Matsuda endpoint with exploratory subgroup marker changes. These observations show target-related physiological action, not a necessary isolated mediator or clinical phenotype crossing; the biomarker inference retains Γ.", "resulting_ceiling": "Γ" }, { "subclaim_id": "SC2", "cap": "Γ", "cap_source": "universal", "triggered": true, "trigger_text_quoted": "Biomarker change without functional/phenotypic change caps at Γ.", "specific_trigger": "The examined 2019 original body explicitly reports unchanged fasting glycemia and HbA1c, alongside improved HOMA/insulin markers. The larger MucT trial reports a null primary insulin-sensitivity endpoint and exploratory marker changes, not a verified full-scope clinically meaningful glycemic/function result. Other live strains, HB05 function and WBF mixtures cannot replace the registered product/population. Genuine 2026 MucT weight-maintenance benefit is separately retained in supplemental SC5.", "resulting_ceiling": "Γ" }, { "subclaim_id": "SC3", "cap": "Γ", "cap_source": "rubric", "triggered": true, "trigger_text_quoted": "Association plus mechanistic in vitro support, or host-pathway plausibility, caps at Γ.", "specific_trigger": "Animal comparisons establish real strain/preparation effects, but directions differ: the one heat-killed preparation tested in 2013 failed, while later non-viable preparations improved selected measures (heat-killed EB-AMDK19 in beagles [7], heat-killed cells in STZ mice [44], and pasteurized preparations), and another species favors live treatment. The live AKK-WST01 human trial has no whole-group HbA1c/weight advantage, with low-baseline exploratory benefit. The HB05 older-adult functional and yogurt studies are genuine different-context results. These do not establish unrestricted clinical transfer across strains, preparations and baseline diseases.", "resulting_ceiling": "Γ" } ], "cap_precedence_resolutions": [ { "collision": "Perturbation in a defined setting versus broader inference", "subclaim_scope_cap_binds_on": "Pasteurized Akkermansia muciniphila MucT supplementation improves clinically meaningful metabolic health in overweight insulin-resistant adults.", "subclaim_scope_threshold_binds_on": "The precise experimentally tested subclaim scope", "resolution": "Recipient animal transfers and strain/factor addition may cross Δ for their actual phenotype and system. Universal cap 5 constrains inference to endogenous human propagation/causation, not a randomized pasteurized-product sufficiency trial. Biomarker cap 4 constrains marker-to-clinical inference for SC1/SC2; it does not cap a positive objective weight-regain intervention in SC5. No weakest-class cap is applied over a complementary same-scope convergent set.", "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": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "Biomarker/host-pathway inference does not establish clinical phenotype or necessary mediation." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "The specified preparation changes selected insulin, lipid and barrier-associated measures in the small 2019 trial, supported by experimental factor/barrier work. The 142-person trial has a null full-population primary Matsuda endpoint with exploratory subgroup marker changes. These observations show target-related physiological action, not a necessary isolated mediator or clinical phenotype crossing; the biomarker inference retains Γ.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC2", "field_valid_perturbation_quote": "\n- Genetic or pharmacologic intervention producing reproducible lifespan/healthspan extension\n- Must separate developmental effects from true aging effects\n- Biomarker change alone does NOT satisfy this threshold", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "No verified positive registered clinical glycemia/function perturbation was examined." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "The examined 2019 original body explicitly reports unchanged fasting glycemia and HbA1c, alongside improved HOMA/insulin markers. The larger MucT trial reports a null primary insulin-sensitivity endpoint and exploratory marker changes, not a verified full-scope clinically meaningful glycemic/function result. Other live strains, HB05 function and WBF mixtures cannot replace the registered product/population. Genuine 2026 MucT weight-maintenance benefit is separately retained in supplemental SC5.", "ceiling_from_boundary_check": "Γ" }, { "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": "", "gamma_hard_rules_triggered": [ "Product/strain and disease generalization remains incomplete." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Animal comparisons establish real strain/preparation effects, but directions differ: the one heat-killed preparation tested in 2013 failed, while later non-viable preparations improved selected measures (heat-killed EB-AMDK19 in beagles [7], heat-killed cells in STZ mice [44], and pasteurized preparations), and another species favors live treatment. The live AKK-WST01 human trial has no whole-group HbA1c/weight advantage, with low-baseline exploratory benefit. The HB05 older-adult functional and yogurt studies are genuine different-context results. These do not establish unrestricted clinical transfer across strains, preparations and baseline diseases.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC4", "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": "", "gamma_hard_rules_triggered": [ "No logical inference from generic taxon/other-product effects to an untested named formula." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Endogenous abundance correlations or an unrelated probiotic effect cannot establish efficacy of an identified commercial formulation. Some directly tested products, including WBF-011, have genuine specific clinical signals, but that is product-specific evidence rather than the proposed generic-to-named inference. This unsupported broad inference is speculative and does not mean every named product is ineffective.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC5", "field_valid_perturbation_quote": "\n- Genetic or pharmacologic intervention producing reproducible lifespan/healthspan extension\n- Must separate developmental effects from true aging effects\n- Biomarker change alone does NOT satisfy this threshold", "qualifying_evidence_present": "yes", "qualifying_evidence_citation": "PMID42120725", "gamma_hard_rules_triggered": [ "Clinical weight regain is an objective phenotype, not merely a biomarker; no Γ hard rule erases its randomized product effect." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "yes", "perturbation_result_note": "The newly examined 90-person randomized trial reports lower 24-week regain with pasteurized MucT than placebo after a diet lead-in. This positive objective clinical phenotype crosses the first human sufficiency threshold for its prespecified maintenance setting. It was not our preregistered primary, does not establish glycemic efficacy in all insulin-resistant adults, and has not yet established generalization or independently replicated maintenance efficacy.", "ceiling_from_boundary_check": "Δ or higher" } ], "thresholds_tested": [ { "subclaim_id": "SC1", "threshold": "Δ", "requirement_quoted": "Requires a transfer paradigm or causal perturbation in vivo.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Isolate the relevant product factor and host pathway at measured human exposure with functional phenotype and mechanism-specific controls." }, { "subclaim_id": "SC2", "threshold": "Δ", "requirement_quoted": "Requires at least one intervention changing lifespan or healthspan in a way consistent with the hypothesis.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Replicate the exact product in baseline-defined overweight insulin-resistant adults with prospectively meaningful HbA1c/glucose/function endpoints over at least 12 weeks and full-population estimands." }, { "subclaim_id": "SC3", "threshold": "Δ", "requirement_quoted": "Requires a transfer paradigm or causal perturbation in vivo.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Directly compare strain/preparation and enroll prespecified disease/baseline strata; reproduce clinical benefit rather than only abundance or marker movement." }, { "subclaim_id": "SC4", "threshold": "Δ", "requirement_quoted": "Requires a transfer paradigm or causal perturbation in vivo.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Test each defined named formulation against matched placebo; mixtures need component subtraction/rescue before claiming Akkermansia necessity." }, { "subclaim_id": "SC5", "threshold": "Δ", "requirement_quoted": "Requires at least one intervention changing lifespan or healthspan in a way consistent with the hypothesis.", "satisfied": "yes", "supporting_evidence": [ "[2] Ninety randomized adults undergoing an eight-week diet followed by 24-week maintenance regained less weight with pasteurized MucT than placebo, 1.2 versus 3.2 kg." ], "what_would_cross_it": "" }, { "subclaim_id": "SC5", "threshold": "Ε", "requirement_quoted": "Requires causal effect in constrained contexts, backgrounds, or species.", "satisfied": "no", "supporting_evidence": [ "[2] Ninety randomized adults undergoing an eight-week diet followed by 24-week maintenance regained less weight with pasteurized MucT than placebo, 1.2 versus 3.2 kg." ], "what_would_cross_it": "Replicate objective maintenance benefit across prespecified baseline clinical contexts and independently assess dietary intake/activity and durability; map boundaries without reclassifying regain failures." } ], "generalization_check": { "generalization_tested": "yes", "context_boundary_mapped": "yes", "internal_negative_controls": [ "2019 fasting glycemia/HbA1c nulls despite insulin/HOMA improvement.", "142-person primary Matsuda null with separate exploratory low-baseline strata.", "58-person live-strain whole-group HbA1c/weight null with subgroup signals.", "Early heat-killed preparation null versus later pasteurized or live preferences.", "Inulin can change weight/insulin need without changing Akkermansia abundance.", "Prediabetes donor fecal transfer fails to reproduce impaired recipient glucose regulation." ], "note": "Preparation, baseline disease and outcome boundaries are visible across originals, but a mapped broad clinical glycemic MucT effect is not established. SC5 is a first positive maintenance context, whose generalization is untested. The lead-in criterion precedes assessed regain and is not a post-regain responder rescue; its post-discovery addition remains explicit. Low-baseline exploratory strata are distinguishable at baseline but require prospective confirmation and interaction/multiplicity checks." }, "falsification_patterns_met": [ { "pattern": "Clinical glycemia does not follow every target-marker improvement", "evidence": "2019 fasting glycemia/HbA1c unchanged despite marker improvements; newer broad trial primary null. This caps the inference without erasing weight-maintenance benefit.", "downgrade_applied": false }, { "pattern": "Microbiota association does not invariably transfer phenotype", "evidence": "Prediabetes donor transfer was null and another correlated taxon had no mouse supplement efficacy.", "downgrade_applied": false } ], "pitfalls_flagged": [ { "pitfall": "Confirmation by biomarker", "where": "HOMA, Matsuda, GLP1 and LPS cannot substitute for registered clinical glycemia/function." }, { "pitfall": "Abundance treated as causality", "where": "Diet-linked abundance and baseline ecology do not validate a named formula." }, { "pitfall": "Selective generalization", "where": "MucT, WST01, HB05, mixtures and yogurt differ in strain, process and eligibility." }, { "pitfall": "Therapeutic effect misread as mechanistic proof", "where": "A true product phenotype does not establish factor or taxon necessity." }, { "pitfall": "Scope fitted to outcome", "where": "Exploratory low-baseline effects remain exploratory; supplemental regain claim is openly post-discovery and nongating." }, { "pitfall": "Replication confused with independence", "where": "The 2019 parent and secondary reports share participants; model-factor successes do not independently establish the human clinical gate." } ], "causal_tally_audit": { "tally_claimed_by_document": 1, "tally_after_audit": 1, "tally_unit": "Positive qualifying study units across scoped subclaims, not independent causal lines or full-claim necessity/sufficiency.", "screened_discriminating_contrasts": 42, "items_rejected": [ "Null and negative contrasts are discriminators, not positive threshold crossings. Reports and replications are not independent causal lines.", "The primary clinical glycemia/function positive tally is zero; supplemental weight-maintenance is one product-specific positive trial unit.", "Different products/strains and diet interventions cannot be counted as direct MucT clinical replication.", "Biomarkers, associations, purified factors and recipient transfers retain their exact system and outcome scope." ] }, "steelman": { "case_one_rung_higher": "Δ for the original primary could be defended by treating insulin-sensitivity improvement as clinically meaningful metabolism or borrowing the positive weight-regain trial. The strongest version would require an actual positive outcome under the preregistered clinical glycemic/function gate; that gate cannot be changed after discovery.", "case_one_rung_lower": "Β could be defended from taxon/health correlations alone, but it would ignore direct product interventions and factor experiments establishing partial-system action. The genuine supplemental weight-maintenance trial independently deserves Δ and must not be flattened into a generic low verdict.", "which_rejected": "Retain Γ for the original clinical glycemia/function primary because markers and different-product outcomes do not cross its fixed gate. Reject a correlation-only Β because controlled product/factor action supplies partial-system evidence. Separately retain Δ for supplemental objective regain benefit rather than using that new endpoint to change preregistered aggregation.", "blocking_cap_threshold_or_missing_experiment": "Missing experiment: A blinded randomized exact-preparation MucT trial enrolls baseline-defined overweight insulin-resistant adults, prespecifies clinically meaningful HbA1c/glucose/function outcomes at 24 weeks, and stratifies low Akkermansia before outcomes with a registered interaction test. Retain full-population estimands and multiplicity controls. A separate replicated 24-week maintenance trial assesses objective regain after a pre-maintenance diet lead-in, with independent outcome/diet/activity measurement and a prespecified durability extension." }, "final_score": { "hsef_level": "Γ", "hsef_descriptor": "Mechanistically plausible, partial system support", "confidence": "Moderate", "confidence_rationale": "Moderate reflects evidence density and reproducibility, not access depth. Fifty-nine primary reports include four human randomized trials, but the registered clinical glycemia/function endpoint rests on one small exploratory pilot with baseline imbalance plus a larger trial whose full-population primary endpoint was null, with benefit confined to exploratory strata; strain, preparation, dose and population differ widely across the animal and comparator work, and the one positive weight-maintenance result is unreplicated. Those are substantive heterogeneity and reproducibility reservations.", "rests_on_non_peer_reviewed_work": false, "rationale": "The original preregistered primary SC2 returns Γ, with Moderate appraisal confidence, because target/insulin-sensitivity effects do not establish the registered clinical glycemia/function benefit. The positive 2026 randomized weight-maintenance finding is separately scored Δ in supplemental SC5. No positive trial is discarded, and no generic class or all-metabolic-benefits negative conclusion is inferred." }, "role_of_mechanism": { "classification": "reinforcing / stabilizing factor", "derivation_step_matched": 5, "derivation": "Administered preparation precedes measured host responses and the separately established maintenance effect; it is not produced by weight regain. Necessity/rate limitation and initiation/removal requirements for a primary driver are unproven. Other interventions alter metabolic trajectories. The coarse step 5 label describes contribution to maintenance/modification of an upstream metabolic state, not endogenous disease primacy.", "tournament_used_as_tiebreaker": false, "note": "Derived from causal direction, not tournament rank." }, "extended_scoring_MSD": { "momentum": { "value": "Mechanistic only", "artifact": "Completed MucT trials expand marker and weight-maintenance evidence, while Amuc_1100/P9 and other factor experiments narrow host pathways. No verified named pending trial addressing the registered clinical glycemia/function threshold was identified in this bounded search.", "justification": "Completed MucT trials expand marker and weight-maintenance evidence, while Amuc_1100/P9 and other factor experiments narrow host pathways. No verified named pending trial addressing the registered clinical glycemia/function threshold was identified in this bounded search." }, "stability": { "value": "Stable", "trigger": "No verified named pending clinical glycemic/function result was identified; future prespecified low-baseline replication could change the claim, but a generic proposed study is not a named pending trigger.", "justification": "No verified named pending clinical glycemic/function result was identified; future prespecified low-baseline replication could change the claim, but a generic proposed study is not a named pending trigger." }, "divergence": { "implied_level": null, "implied_level_basis": "Marker, weight-maintenance and commercial strain/abundance framings describe different claims; no single measured field-implied ladder level applies.", "assessed_level": "Γ", "gap_in_rungs": null, "value": "Contested", "justification": "No invented field consensus or numeric belief gap is inferred from provider output or generic supplement promotion." }, "calibration_note": "M/S/D never modify HSEF level or confidence." }, "change_record": { "applies": false, "prior_level": "none assigned", "prior_confidence": null, "prior_source": null, "derived_before_consulting_prior": true, "new_level": "Γ", "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": "A blinded randomized exact-preparation MucT trial enrolls baseline-defined overweight insulin-resistant adults, prespecifies clinically meaningful HbA1c/glucose/function outcomes at 24 weeks, and stratifies low Akkermansia before outcomes with a registered interaction test. Retain full-population estimands and multiplicity controls. A separate replicated 24-week maintenance trial assesses objective regain after a pre-maintenance diet lead-in, with independent outcome/diet/activity measurement and a prespecified durability extension.", "readout": "Clinical glycemic control/function and adverse events for the original primary; objective regain for supplemental SC5; insulin/GLP1/barrier markers are secondary mechanistic leads.", "critical_control": "Matched product identity, process, dose, placebo, medications and diet/activity; prospective interaction and full-population analyses, not selection of outcome-defined responders; component controls for mechanism claims.", "supporting_result": "A clinically meaningful exact-product randomized glycemic/function result crosses the original first threshold; replicated maintenance benefit maps SC5 context and improves its generalization evidence.", "falsifying_result": "Marker movement without clinical benefit leaves SC2 uncrossed; a maintenance replication null maps a boundary without negating other verified context-specific results." } ], "knowledge_gaps": [ { "name": "Gap 1", "statement": "Prospectively meaningful clinical glycemic/function efficacy of exact pasteurized MucT over at least 12 weeks.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 2", "statement": "Independent maintenance replication and longer durability after a clearly defined pre-maintenance diet lead-in.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 3", "statement": "Prespecified baseline-low interactions with multiplicity control rather than within-subgroup significance comparisons.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 4", "statement": "Direct strain/preparation and commercial-product identity comparisons; named mixture success is not component necessity.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 5", "statement": "Necessary human factor/barrier mediator testing, distinct from purified factor sufficiency in mice.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 6", "statement": "Complete body/supplement review and long-term safety beyond small short trial populations.", "relevance": "Limits mechanism identification or scope." } ], "review_metadata": { "review_date": "2026-10-13", "reviewer": "Codex", "evidence_base_note": "59 primary reports; literature cutoff 2026-10-13; source examination UTC date 2026-10-13; bounded critical review, not exhaustive systematic review.", "literature_tools_available": true, "literature_tools_note": "Life Sciences Literature PubMed/Entrez, separately logged public original-body retrieval, and Consensus Pro browser searches. Provider output retained as observed browser text with citation-link mappings, or as previously exported connector documents where present. AI synthesis is not primary full-text verification. Consensus retrieved/included counts are not examined-primary counts. Scite monthly limit was reached earlier in this session; no new Scite query or incoming citation-context audit is claimed for these cases. Tool receipts record actual use. Supplementary discovery outputs do not earn primary-count credit. No independent blinded review.", "skill_version": "5.3", "validator_run": "PASS: exact archived HSEF v5.3 validator rerun after final sealing.", "validator_warnings_addressed": "No warnings.", "limits": "Bounded source-based critical review; no complete-paper/supplement audit, independent scientific peer review or blinded calibration. Revision cases retain original prose outside the three framework output blocks and have explicit correction logs.", "adversarial_reviews": [ { "date": "2026-10-14", "reviewer": "Claude Opus 5.5 (Anthropic)", "authoring_model": "Sol 6.1", "findings_applied": [ "A1", "A2", "A3", "A4" ], "level_after": "Γ", "confidence_after": "Moderate" }, { "date": "2026-11-02", "reviewer": "Claude Opus 5.5 (Anthropic)", "authoring_model": "Sol 6.1", "findings_applied": [ "A5", "A6", "A7", "A8", "A9", "A10", "A11" ], "level_after": "Γ", "confidence_after": "Moderate", "record": "ADVERSARIAL_REVIEW.akkermansia-metabolic-health.md; adversarial-findings.akkermansia-metabolic-health.json", "pmids_verified": "59/59" } ] }, "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": "These topic families were selected from an editorial traffic-priority list. Selection was visible; no blind calibration or predetermined clinical verdict was preregistered." }, "upper_ladder_check": { "final_level_below_zeta": true, "equivalents_considered": [ { "kind": "mendelian_randomization", "available": false, "why_not_sufficient": "Exact strain/factor intervention and controlled clinical products make higher rungs reachable. However, the human primary clinical glycemic result, prospective subgroup replication and isolated necessary mediator are missing. A single positive maintenance trial crosses Δ in its supplemental scope but not independent convergence. Abundance and murine transfer cannot supply these human gates." }, { "kind": "natural_experiment", "available": false, "why_not_sufficient": "Exact strain/factor intervention and controlled clinical products make higher rungs reachable. However, the human primary clinical glycemic result, prospective subgroup replication and isolated necessary mediator are missing. A single positive maintenance trial crosses Δ in its supplemental scope but not independent convergence. Abundance and murine transfer cannot supply these human gates." }, { "kind": "dose_response_across_populations", "available": false, "why_not_sufficient": "Exact strain/factor intervention and controlled clinical products make higher rungs reachable. However, the human primary clinical glycemic result, prospective subgroup replication and isolated necessary mediator are missing. A single positive maintenance trial crosses Δ in its supplemental scope but not independent convergence. Abundance and murine transfer cannot supply these human gates." }, { "kind": "withdrawal_rechallenge", "available": true, "why_not_sufficient": "Exact strain/factor intervention and controlled clinical products make higher rungs reachable. However, the human primary clinical glycemic result, prospective subgroup replication and isolated necessary mediator are missing. A single positive maintenance trial crosses Δ in its supplemental scope but not independent convergence. Abundance and murine transfer cannot supply these human gates." }, { "kind": "therapeutic_perturbation_hard_endpoint", "available": false, "why_not_sufficient": "Exact strain/factor intervention and controlled clinical products make higher rungs reachable. However, the human primary clinical glycemic result, prospective subgroup replication and isolated necessary mediator are missing. A single positive maintenance trial crosses Δ in its supplemental scope but not independent convergence. Abundance and murine transfer cannot supply these human gates." } ], "convergence_present": false, "cap_reapplied_to_convergent_set": false }, "provenance_header": { "sources_total": 59, "claims_total": 65, "claims_verified": 65, "claims_unverified": 0, "claims_contradicted": 0, "tier_a_sources": 59, "generated_by": "Codex; HSEF v5.3", "gate_passed": true }, "claims": [ { "id": "C1", "text": "The 40-enrolled/32-completed pilot found pasteurized Akkermansia improved insulin-sensitivity, insulin and cholesterol measures over three months; weight and fat differences were nonsignificant. Small exploratory biomarker effects do not establish clinical glycemic control/function; live/pasteurized arms and parent-trial secondary reports require shared-study grouping.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 1 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 0:Online Methods:paragraph0, 0:Online Methods:paragraph1, 0:Online Methods:paragraph2, 0:Online Methods:paragraph3, 0:Online Methods:paragraph7, 0:Online Methods:paragraph8, 7:Main text (unsectioned body paragraphs):paragraph3, 7:Main text (unsectioned body paragraphs):paragraph4, 7:Main text (unsectioned body paragraphs):paragraph5, 7:Main text (unsectioned body paragraphs):paragraph9, 7:Main text (unsectioned body paragraphs):paragraph13, 7:Main text (unsectioned body paragraphs):paragraph14. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C2", "text": "Ninety randomized adults undergoing an eight-week diet followed by 24-week maintenance regained less weight with pasteurized MucT than placebo, 1.2 versus 3.2 kg. Genuine weight-maintenance benefit is not erased; baseline insulin-resistance eligibility and registered clinical glycemia/function endpoint require separate scope assessment, and active components were not isolated.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3", "SC5" ], "source_ns": [ 2 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C3", "text": "A 100-person 12-week older-adult HB05 trial reported improved left-leg extensor torque and follistatin compared with placebo. Different strain and older functional population cannot establish MucT metabolic efficacy or all-strain generalization; a measured growth mediator is not necessity.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 3 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:2. Materials and Methods:paragraph1, 1:2. Materials and Methods:paragraph2, 1:2. Materials and Methods:paragraph3, 1:2. Materials and Methods:paragraph5, 2:3. Results:paragraph0, 2:3. Results:paragraph2, 2:3. Results:paragraph3, 2:3. Results:paragraph4, 2:3. Results:paragraph5. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C4", "text": "A 142-person four-month MucT multicenter trial had a null primary Matsuda endpoint; subsequent exploratory baseline-low Akkermansia analyses found selected marker benefits. Do not replace full-population null with an unconfirmed subgroup; GLP1/insulin-sensitivity proxies and weight P=.06 do not establish registered clinical glycemia/function benefit.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 4 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C5", "text": "Secondary analysis of the pilot found no global endocannabinoidome change, with selected mono-palmitoylglycerol changes and PPARalpha activity support. Shares parent trial; univariate lipid differences and receptor activity do not isolate necessary human mediation or clinical benefit.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 5 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C6", "text": "Pasteurized bacteria and purified Amuc_1100 improved metabolic/barrier measures in obese/diabetic mice; the protein interacts with TLR2 and partially reproduces effects. Mouse administration and a purified factor establish experimental sufficiency, not endogenous human necessity or clinically meaningful human outcomes.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 6 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C7", "text": "Heat-killed EB-AMDK19 reduced diet-induced weight/fat/triglyceride gain in beagles over 12 weeks. Different strain and canine prevention setting cannot establish human MucT clinical efficacy or universal pasteurized/live equivalence.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 7 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C8", "text": "Live/pasteurized Akk11 improved adiposity and barrier measures in HFD mice with different microbial and fatty-acid responses. Single-strain mouse exposure and differing fermentation responses do not establish formulation interchangeability in human clinical disease.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 8 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C9", "text": "Two strains in live/pasteurized form improved 12-week HFD mouse metabolic measures; pasteurized forms improved glucose tolerance more. Mouse formulation comparison maps context, not human universal equivalence; administered microbes do not prove endogenous necessity.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 9 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C10", "text": "Live/pasteurized MucT and vesicles reduced HFD obesity/metabolic measures, with stronger selected effects for pasteurized cells and vesicles. Food intake and broad microbiota changes are alternative mediators; vesicle/preventive mouse effects cannot establish human clinical control or factor necessity.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 10 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C11", "text": "A novel Akkermansia species improved mouse weight/fat/insulin measures, with live form more effective than pasteurized. Different species and opposite formulation preference limit universal pasteurization superiority; no direct human MucT endpoint.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 11 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C12", "text": "AKM Lab-01 live/processed preparations improved diet-induced mouse obesity/metabolic measures and had a mouse dietary safety study. Calculated human safety extrapolation is not a human clinical trial or evidence of all-product long-term safety/equivalence.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 12 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C13", "text": "A six-month multi-strain plus fructooligosaccharide PCOS trial improved menstrual regularity, selected androgen/waist and quality-of-life outcomes with matched lifestyle advice. Mixture-specific benefits do not establish MucT or every marketed probiotic; not all listed metabolic endpoints were positive.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 13 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C14", "text": "Lactobacillus casei Shirota fermented milk reduced measured bacterial translocation and changed fecal communities in 70 diabetic adults over 16 weeks. No-probiotic control and translocation endpoint do not establish MucT clinical glycemic benefit; blood microbial assays require contamination care.", "carries_number": true, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 14 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C15", "text": "Six-week Bifidobacterium TISTR 2591 crossover attenuated a fasting-glucose rise and changed selected insulin/lipid measures, with no body-composition change. Different strain, short duration and modest comparator deterioration cannot establish the 12-week MucT clinical claim or generic-product efficacy.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 15 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C16", "text": "Twelve-week multi-strain supplementation alleviated metformin GI symptoms but did not add metabolic/anthropometric benefit in 30 insulin-resistant women. Metformin-associated within-group improvements are not probiotic treatment effects; symptom benefit does not establish MucT clinical metabolism.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 16 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C17", "text": "Different probiotic strains altered selected plasma bile acids but not glucose, insulin or serum lipids in a placebo crossover study. Biochemical target movement is not clinical efficacy and the strains are not MucT; washout/period and subset context remain relevant.", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 17 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C18", "text": "Eight-week HAC01 trial in 40 prediabetic adults improved two-hour glucose/HbA1c versus placebo while several insulin/microbiota endpoints remained null. A genuine different-strain clinical effect does not validate MucT or an unnamed commercial formula; duration is below its registered gate.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 18 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C19", "text": "Four-week L.reuteri in 21 glucose-tolerant adults increased incretin/insulin secretion without altering clamp insulin sensitivity, mass or ectopic fat. Target engagement does not establish improved phenotype or MucT-specific mechanism; short and distinct exposure cannot support universal probiotics.", "carries_number": true, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 19 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C20", "text": "Twelve-week L.salivarius Ls33 trial in 50 obese adolescents found no metabolic, inflammatory or anthropometric improvement versus placebo. A product/context-specific null is a generalization boundary, not a refutation of MucT or every probiotic strain.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 20 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C21", "text": "Multi-strain pregnancy trial found no metabolic/inflammatory or newborn-composition benefit despite high completion. Pregnancy, mixture and developmental endpoints differ from MucT adult treatment; nulls cannot be erased by target presence.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 21 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C22", "text": "Twelve-week six-strain post-GDM trial reported modest fasting-glucose and HbA1c/lipid differences with microbiota shifts. Mixture-specific biochemical/clinical glycemia effects cannot establish MucT identity or necessary microbiota mediation; long-term prevention was not demonstrated.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 22 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C23", "text": "Eight-week four-strain GDM trial found greater fasting-glucose decline and late weight-gain differences, but adjusted sensitivity comparison was null. Pregnancy-specific exposure and short horizon do not establish MucT or generic probiotics; within- versus between-group endpoints must remain separate.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 23 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C24", "text": "Two strains plus octacosanol altered CRP/ghrelin in obese women over 12 weeks but did not change BMI between groups. Bundled active ingredient and marker-only changes cannot establish bacterial necessity, MucT clinical benefit or all-product efficacy.", "carries_number": true, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 24 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C25", "text": "Eight-week multispecies trial reported attenuated fasting-glucose/HOMA rise and selected inflammatory/antioxidant changes. Parent record has expression of concern PMID37334997; this flagged short mixture study is not used as decisive support or generalized to MucT.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 25 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C26", "text": "B.breve crossover in obese youths found carryover requiring first-period analysis, with selected insulin-sensitivity changes but no cytokine/GLP1 shift. Carryover and interval uncertainty constrain inference; childhood, strains and marker outcomes cannot establish MucT or universal efficacy.", "carries_number": true, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 26 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C27", "text": "Oats versus rice in 210 adults reduced selected cholesterol fractions and increased Akkermansia/Roseburia abundance over 45 days. Dietary components and correlated taxa do not isolate Akkermansia necessity or supplement-specific efficacy; both groups improved some lipids.", "carries_number": true, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 27 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C28", "text": "A 30-person multifunctional cereal crossover reduced local inflammation/endotoxemia and shifted microbiota, with unchanged cardiometabolic markers. Multi-ingredient diet and marker movement cannot demonstrate a named probiotic clinical effect or bacterial mediation.", "carries_number": true, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 28 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C29", "text": "High/normal-protein calorie restriction in 80 obese adults altered microbiota; both diets enriched Akkermansia and Bifidobacterium. Diet-induced microbial abundance may accompany treatment response rather than cause it; no MucT product or necessity contrast.", "carries_number": true, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 29 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C30", "text": "A 34-person crossover of early high-fiber/energy-restricted nutrition improved clinical glycemia and shifted several taxa including Akkermansia. Bundled energy restriction and sequence persistence preclude isolated fiber or taxon mediation; relative HbA1c-change percentages are not absolute percentage-point reductions.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 30 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C31", "text": "Eight-week prebiotic blend increased relative Akkermansia abundance in a per-protocol subset, with a trend in GI comfort. Seventy randomized but fifty per-protocol; abundance increase and trend do not establish clinical metabolic benefit or MucT supplement efficacy.", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 31 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C32", "text": "Four-week resistant potato starch improved bowel-pattern measures and increased relative Bifidobacterium/Akkermansia versus placebo. Short prebiotic laxation/abundance effects are distinct from MucT clinical metabolism and do not isolate one taxon's necessity.", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 32 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C33", "text": "Dietary analyses within a weight-loss trial associated fiber with fecal acetate and fructose inversely with Akkermansia in young adults with T1D. Nonrandomized diet/taxon associations and limited repeated sampling do not establish MucT efficacy or a universal fiber-to-Akkermansia pathway.", "carries_number": true, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 33 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C34", "text": "Three-month inulin plus insulin in 49 T1D adults modestly reduced weight/insulin need but did not improve HbA1c/CGM or Akkermansia levels versus insulin alone. A fiber clinical change can occur without increased Akkermansia; different diabetes and product context cannot establish pasteurized MucT efficacy.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 34 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C35", "text": "Pooled secondary breast-cancer weight-loss trial analysis associated baseline Akkermansia with adiposity and fiber change in low-abundance participants. Randomized diet does not randomize bacterial abundance; small disease-selected associations cannot prove taxon mediation or named-product clinical efficacy.", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 35 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C36", "text": "Resistant starch and polydextrose had distinct bile-acid effects, with fiber-specific Akkermansia correlations in the DISC trial. Biochemical correlations are not necessary microbial mediation or clinical metabolic health; formulations cannot be grouped as uniform fiber effects.", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 36 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C37", "text": "An isoenergetic Mediterranean-diet trial improved postprandial glucose responses with SCFA and Akkermansia shifts over eight weeks. Whole-diet composition and short horizon cannot identify Akkermansia-specific causal contribution or validate a MucT product.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 37 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C38", "text": "Four-week barley beta-glucan bread changed cholesterol/SCFA measures; baseline taxa differed in cholesterol responders. Within-group cholesterol change and post-outcome responder classification cannot establish between-group clinical microbial causality or define an unfalsifiable subgroup.", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 38 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C39", "text": "Live Akkermansia reversed HFD metabolic abnormalities in mice, whereas the tested heat-killed preparation did not; prebiotic normalization correlated with improved measures. Heat-killed and later pasteurized preparation protocols are not identical; experimental sufficiency does not prove endogenous human necessity or universal live superiority.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 39 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C40", "text": "Twelve-week live AKK-WST01 trial in 58 overweight/obese T2D adults had no whole-group HbA1c or weight advantage; low-baseline exploratory participants showed selected benefit and colonization. Different live strain and subgroup contrasts cannot establish broad pasteurized MucT efficacy; within-subgroup significance is not automatically an interaction or independent replicated subgroup.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 40 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C41", "text": "Purified P9 increased GLP1/thermogenesis in mice and cells; IL6 deficiency abolished selected glucose-homeostasis effects and altered its receptor pathway. Factor sufficiency and a knockout narrow an experimental mechanism, but do not establish that P9 mediates human pasteurized MucT clinical outcomes.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 41 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C42", "text": "In a 49-person calorie-restriction/stabilization cohort, higher baseline Akkermansia associated with healthier status and better metabolic response while abundance subsequently declined. Diet and bacterial abundance are not independently randomized; a decrease alongside improvement limits a simple more-is-better abundance interpretation.", "carries_number": true, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 42 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C43", "text": "Twelve-week WBF-011 mixture trial in 76 T2D adults improved postprandial glucose primary outcome and reported lower HbA1c relative to placebo. The five-strain/inulin product is genuinely trialed but cannot identify Akkermansia component necessity or validate MucT, another formula or every probiotic.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 43 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C44", "text": "Heat-killed Akkermansia improved STZ-mouse metabolic/muscle signaling, with intestinal IGF2 secretion and downstream muscle effects. Survival-selected STZ context and experimental heat-killed treatment are not a pasteurized MucT human functional trial or mediator necessity demonstration.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 44 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C45", "text": "Akkermansia improved HFD zebrafish weight/survival and barrier measures; antibiotic pretreatment partly abolished selected effects with tryptophan/AhR changes. Broad antibiotics and metabolite associations do not isolate the exact human product or necessary human mediator; species and diet context remain explicit.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 45 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C46", "text": "Intestinal FABP1 knockout and microbiota depletion narrowed lipid-absorption biology; Akkermansia supplementation and L-norleucine inhibited selected obesity/fatty-acid outcomes. A bacterial abundance/metabolite link and factor sufficiency do not establish human pasteurized MucT glycemic efficacy or endogenous bacterial necessity.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 46 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C47", "text": "MASLD cohort of 122 associated Akkermansia with GGT, HDL and glycemia but not ALT or AST. Clinical/taxon correlations and speculative oxidative-stress interpretation cannot establish product efficacy or microbial mediation.", "carries_number": true, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 47 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C48", "text": "Six-week live MucT in HFD mice reduced adiposity and changed mucus glycans/barrier markers without changing overall microbiota or mucus thickness. Living mouse supplement effects do not establish pasteurized human clinical efficacy; a mucus-composition association is not necessary mediator ablation.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 48 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C49", "text": "Prediabetes case-control microbiota had lower Akkermansia; fecal transfers from prediabetic/drug-naive diabetic donors did not impair recipient glucose regulation. A whole-community transfer null does not refute all Akkermansia product effects, but association cannot be counted as transferable glucose disease.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3", "SC4" ], "source_ns": [ 49 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C50", "text": "Eight-week Akkermansia-postbiotic yogurt in 66 randomized adults improved selected waist, fat, AST and appetite outcomes versus low-fat yogurt; L.rhamnosus yogurt did not. Different formulation/strain details, multiple endpoints and short horizon cannot validate MucT's registered clinical glycemic/function claim; genuine context positives are retained.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 50 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C51", "text": "Akkermansia-derived LPS improved obese-mouse measures; IL22 neutralization eliminated selected antiobesity effects with TLR4/IL23 pathway evidence. Intraperitoneal purified LPS and acute mouse toxicity comparison are not oral MucT human efficacy or universal bacterial-LPS safety.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 51 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C52", "text": "Akkermansia/Amuc_1100 reduced HFD mouse weight/liver injury and metabolic measures with atorvastatin as a positive comparator. Broad gut/liver changes and factor administration do not establish human clinical glycemic/function effects or a unique necessary pathway.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 52 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C53", "text": "Akkermansia vesicles improved HFD mouse weight/glucose tolerance and cell barrier function; E.coli vesicles did not reproduce selected barrier effects. Vesicle sufficiency and experimental positive/negative control do not establish intact pasteurized MucT clinical efficacy or vesicle necessity in humans.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 53 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C54", "text": "Akkermansia and L-aspartate improved HFC-mouse fatty-liver measures, with persistent effects after withdrawal and partial antibiotic attenuation. Broad antibiotic, metabolite and liver-pathology contrasts do not isolate the human product or convert a model-specific liver result to clinical glycemic control.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 54 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C55", "text": "Mouse/germ-free studies and AMPK deficiency support an Akkermansia-acetate pathway reducing selected hepatic ferroptotic injury measures. AMPK dependence and colonization narrow animal factor biology; no human clinical MucT endpoint or mediator necessity is established.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 55 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C56", "text": "Subdoligranulum abundance associated with healthier human metabolic measures, but its cultured-strain supplementation did not improve eight-week obese/diabetic mouse outcomes. A clear association-to-intervention boundary for another taxon cannot establish MucT inefficacy; it warns against generic abundance/product inference.", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 56 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C57", "text": "Batf3 deficiency altered barrier/immune/microbiota state and metabolic syndrome; antibiotic and glycolysis interventions changed selected outcomes. Developmental host-gene perturbation and broad antibiotics cannot attribute syndrome specifically to Akkermansia or demonstrate human product efficacy.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 57 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C58", "text": "Human colonic organoid co-culture with goblet-cell-deficient controls showed mucin-dependent Akkermansia transcription and host-interaction genes. A model-specific microbial transcription response is not clinical metabolism or proof of pasteurized human-product mechanism.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 58 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C59", "text": "Cell-based mucin arrays identify O-glycan-specific Akkermansia binding retained after pasteurization, with neuraminidase revealing binding epitopes. Adhesion survives processing but colonization/function and clinical glycemic benefit are not thereby established.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 59 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "CSC1", "text": "The specified preparation changes selected insulin, lipid and barrier-associated measures in the small 2019 trial, supported by experimental factor/barrier work. The 142-person trial has a null full-population primary Matsuda endpoint with exploratory subgroup marker changes. These observations show target-related physiological action, not a necessary isolated mediator or clinical phenotype crossing; the biomarker inference retains Γ.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 14, 17, 19, 24, 26, 27, 28, 29, 31, 32, 33, 35, 36, 38, 39, 41, 42, 44, 45, 46, 47, 48, 49, 51, 52, 53, 54, 55, 56, 57, 58, 59 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CSC2", "text": "The examined 2019 original body explicitly reports unchanged fasting glycemia and HbA1c, alongside improved HOMA/insulin markers. The larger MucT trial reports a null primary insulin-sensitivity endpoint and exploratory marker changes, not a verified full-scope clinically meaningful glycemic/function result. Other live strains, HB05 function and WBF mixtures cannot replace the registered product/population. Genuine 2026 MucT weight-maintenance benefit is separately retained in supplemental SC5.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 1, 2, 3, 4, 6, 7, 15, 16, 18, 20, 21, 22, 23, 25, 30, 34, 37, 40, 43, 50 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CSC3", "text": "Animal comparisons establish real strain/preparation effects, but directions differ: the one heat-killed preparation tested in 2013 failed, while later non-viable preparations improved selected measures (heat-killed EB-AMDK19 in beagles [7], heat-killed cells in STZ mice [44], and pasteurized preparations), and another species favors live treatment. The live AKK-WST01 human trial has no whole-group HbA1c/weight advantage, with low-baseline exploratory benefit. The HB05 older-adult functional and yogurt studies are genuine different-context results. These do not establish unrestricted clinical transfer across strains, preparations and baseline diseases.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 39, 40, 41, 43, 44, 45, 46, 48, 49, 50, 51, 52, 53, 54, 55, 57, 58, 59 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CSC4", "text": "Endogenous abundance correlations or an unrelated probiotic effect cannot establish efficacy of an identified commercial formulation. Some directly tested products, including WBF-011, have genuine specific clinical signals, but that is product-specific evidence rather than the proposed generic-to-named inference. This unsupported broad inference is speculative and does not mean every named product is ineffective.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 42, 43, 47, 49, 50, 56 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CSC5", "text": "The newly examined 90-person randomized trial reports lower 24-week regain with pasteurized MucT than placebo after a diet lead-in. This positive objective clinical phenotype crosses the first human sufficiency threshold for its prespecified maintenance setting. It was not our preregistered primary, does not establish glycemic efficacy in all insulin-resistant adults, and has not yet established generalization or independently replicated maintenance efficacy.", "carries_number": false, "load_bearing_for": [ "SC5" ], "source_ns": [ 2 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CH", "text": "Pasteurized MucT reduced weight regain in a 2026 trial; broader clinical glycemic benefits and interchangeability with other products remain unestablished.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 2, 1, 4, 40, 43 ], "verification": "verified", "verified_against": "Bounded synthesis of examined sources; score is adjudication.", "verified_on": "2026-10-13", "note": "" } ], "citation_ledger": [ { "n": 1, "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.", "tier": "A", "kind": "rct", "pmid": "31263284", "doi": "10.1038/s41591-019-0495-2", "url": "https://pubmed.ncbi.nlm.nih.gov/31263284/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MUCT-NCT02637115", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 0:Online Methods:paragraph0, 0:Online Methods:paragraph1, 0:Online Methods:paragraph2, 0:Online Methods:paragraph3, 0:Online Methods:paragraph7, 0:Online Methods:paragraph8, 7:Main text (unsectioned body paragraphs):paragraph3, 7:Main text (unsectioned body paragraphs):paragraph4, 7:Main text (unsectioned body paragraphs):paragraph5, 7:Main text (unsectioned body paragraphs):paragraph9, 7:Main text (unsectioned body paragraphs):paragraph13, 7:Main text (unsectioned body paragraphs):paragraph14. No complete-paper or supplement audit claimed.", "carries_claims": [ "C1", "CSC1", "CSC2", "CSC3", "CH" ] }, { "n": 2, "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.", "tier": "A", "kind": "rct", "pmid": "42120725", "doi": "10.1038/s41591-026-04394-7", "url": "https://pubmed.ncbi.nlm.nih.gov/42120725/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MUCT-NCT05417360", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C2", "CSC1", "CSC2", "CSC3", "CSC5", "CH" ] }, { "n": 3, "citation": "Kang CH, Jung ES, Jung SJ et al. Pasteurized Akkermansia muciniphila HB05 (HB05P) Improves Muscle Strength and Function: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients. 2024.", "tier": "A", "kind": "rct", "pmid": "39683431", "doi": "10.3390/nu16234037", "url": "https://pubmed.ncbi.nlm.nih.gov/39683431/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID39683431", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:2. Materials and Methods:paragraph1, 1:2. Materials and Methods:paragraph2, 1:2. Materials and Methods:paragraph3, 1:2. Materials and Methods:paragraph5, 2:3. Results:paragraph0, 2:3. Results:paragraph2, 2:3. Results:paragraph3, 2:3. Results:paragraph4, 2:3. Results:paragraph5. No complete-paper or supplement audit claimed.", "carries_claims": [ "C3", "CSC2", "CSC3" ] }, { "n": 4, "citation": "Suenaert P, Segers A, Rymenans L et al. Effect of pasteurized Akkermansia muciniphila MucT on insulin sensitivity, body composition, and GLP-1 production in subjects with metabolic syndrome: impact of low baseline gut Akkermansia levels. Gut microbes. 2026.", "tier": "A", "kind": "rct", "pmid": "42343233", "doi": "10.1080/19490976.2026.2690689", "url": "https://pubmed.ncbi.nlm.nih.gov/42343233/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MUCT-NCT05114018", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C4", "CSC1", "CSC2", "CSC3", "CH" ] }, { "n": 5, "citation": "Depommier C, Vitale RM, Iannotti FA et al. Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists. Cells. 2021.", "tier": "A", "kind": "rct", "pmid": "33477821", "doi": "10.3390/cells10010185", "url": "https://pubmed.ncbi.nlm.nih.gov/33477821/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MUCT-NCT02637115", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C5", "CSC1", "CSC3" ] }, { "n": 6, "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. 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Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "Association plus cell-culture metabolite assays", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "Association plus in vitro immune readouts", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "Any framework that has not crossed the transfer/rescue threshold in vivo", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC5", "rule_quoted": "ROS change measurements alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC5", "rule_quoted": "NAD level change measurements alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC5", "rule_quoted": "Mitochondrial metrics alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC5", "rule_quoted": "Senescence marker changes alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC5", "rule_quoted": "Single-species or single-strain evidence", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC5", "rule_quoted": "Biomarker-only improvement without organismal benefit", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." } ], "supplemental_subclaim_after_discovery": { "id": "SC5", "added_utc": "2026-10-13T16:18:20.009325+00:00", "preregistered": false, "reason": "The newly examined 2026 original PMID42120725 demonstrates weight-maintenance benefit. Preserve that genuine positive finding as a separately scored non-gating claim rather than expanding the preregistered glycemic/function primary endpoint retrospectively.", "primary_aggregation_unchanged": true, "source_first_examined_receipt": "examinations/original-0-8-10000.json", "antecedent_scope_note": "The diet lead-in weight-loss criterion is known before the assessed maintenance/regain outcome, not a retrospective exclusion of regain failures." }, "consensus_validation": { "completed": true, "status": "completed_original_source_reconciliation", "provider_mode": "Consensus Pro signed-in browser; observed output and citation link mappings", "queries": [ "https://consensus.app/search/akkermansia-muciniphila-glycemic-control/og3g0CWlR86FlNlylN1O6g/" ], "query_record_note": "Exact provider question/response retained privately in its retrieval receipt.", "primary_comparison_count": 8, "primary_comparisons": [ { "pmid": "31263284", "doi": "10.1038/s41591-019-0495-2", "source_type": "primary study report", "study_group": "MUCT-NCT02637115", "access_depth": "full_text_partial", "consensus_aspect": "Pilot marker benefit versus clinical glycemia", "result_comparison": "Consensus reports improved insulin/HOMA with unchanged fasting glycemia/HbA1c. Selected original Methods and Results independently confirm HOMA calculation, unchanged fasting glycemia and HbA1c, and a not-markedly-hyperglycemic baseline. These clinical nulls do not erase the genuine marker effects or demonstrate ineffectiveness in every population.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/31263284/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\akkermansia-metabolic-health\\examinations\\original-0-8-10000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\akkermansia-metabolic-health\\body-presentation-receipts\\31263284-s0-p0-1-2-3-7-8.json", "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\akkermansia-metabolic-health\\body-presentation-receipts\\31263284-s7-p3-4-5-9-13-14.json" ] }, { "pmid": "31263284", "doi": "10.1038/s41591-019-0495-2", "source_type": "primary study report", "study_group": "MUCT-NCT02637115", "access_depth": "full_text_partial", "consensus_aspect": "Baseline imbalance and analyzed participants", "result_comparison": "Consensus identifies 40 enrolled and 32 completers. The original body confirms 11 placebo, 12 pasteurized and nine live completers after personal, antibiotic-use and protocol exclusions, with higher insulin/lower sensitivity in the pasteurized group at baseline. This imbalance and completion analysis limit a definitive clinical interpretation; the provider summary does not replace those Methods details.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/31263284/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\akkermansia-metabolic-health\\examinations\\original-0-8-10000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\akkermansia-metabolic-health\\body-presentation-receipts\\31263284-s0-p0-1-2-3-7-8.json", "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\akkermansia-metabolic-health\\body-presentation-receipts\\31263284-s7-p3-4-5-9-13-14.json" ] }, { "pmid": "42343233", "doi": "10.1080/19490976.2026.2690689", "source_type": "primary study report", "study_group": "MUCT-NCT05114018", "access_depth": "abstract_metadata", "consensus_aspect": "Larger trial primary null and exploratory scope", "result_comparison": "Consensus describes the 142-person trial primary Matsuda null with subsequent low-baseline marker signals. The examined original abstract confirms the intention-to-treat primary null and labels subsequent analyses exploratory, including weight P=.06 in low-baseline participants. We did not obtain its complete Methods/Results through the attempted public route, so detailed recruitment disruptions and full analysis-plan claims in the provider are not treated as independently verified body findings.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/42343233/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\akkermansia-metabolic-health\\examinations\\original-0-8-10000.json" ], "body_receipts": [] }, { "pmid": "42120725", "doi": "10.1038/s41591-026-04394-7", "source_type": "primary study report", "study_group": "MUCT-NCT05417360", "access_depth": "abstract_metadata", "consensus_aspect": "Genuine product-specific weight-maintenance benefit", "result_comparison": "Consensus correctly preserves lower 24-week regain after an eight-week diet lead-in. The original abstract confirms 90 participants, the maintenance outcome and lower regain with MucT than placebo. This is openly scored as supplemental SC5 added after discovery; the primary glycemic/function gate remains unchanged. Pre-maintenance lead-in eligibility precedes assessed regain and does not exclude later regain failures retrospectively.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/42120725/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\akkermansia-metabolic-health\\examinations\\original-0-8-10000.json" ], "body_receipts": [] }, { "pmid": "39683431", "doi": "10.3390/nu16234037", "source_type": "primary study report", "study_group": "PMID39683431", "access_depth": "full_text_partial", "consensus_aspect": "Different-strain function and absence of measurement", "result_comparison": "The provider says direct human trials show no measurable physical-function gains while citing MucT metabolic/maintenance studies and does not use HB05 as a named supporting anchor. A missing endpoint is not a tested null. Our selected HB05 original Methods/Results show a different strain in older adults, positive left/combined extensor torque, unchanged grip and myostatin, and per-protocol analysis. Those positives remain real but cannot be extrapolated to MucT clinical metabolism.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/39683431/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\akkermansia-metabolic-health\\examinations\\original-0-8-10000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\akkermansia-metabolic-health\\body-presentation-receipts\\39683431-s1-p1-2-3-5.json", "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\akkermansia-metabolic-health\\body-presentation-receipts\\39683431-s2-p0-2-3-4-5.json" ] }, { "pmid": "32675291", "doi": "10.1136/bmjdrc-2020-001319", "source_type": "primary study report", "study_group": "WBF-NCT03893422", "access_depth": "abstract_metadata", "consensus_aspect": "Review-mediated mixture statement checked against its original", "result_comparison": "Consensus supports its multi-strain glucose/HbA1c statement through review/mechanism citations. Our examined WBF-011 original instead supplies the direct 76-person 12-week trial: the five-strain/inulin mixture improves postprandial glucose and reports a HbA1c signal. This specific product evidence cannot isolate Akkermansia component necessity or validate other commercial formulas. Reviews do not add primary-count credit.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/32675291/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\akkermansia-metabolic-health\\examinations\\original-38-46-10000.json" ], "body_receipts": [] }, { "pmid": "39879980", "doi": "10.1016/j.cmet.2024.12.010", "source_type": "primary study report", "study_group": "WST01-NCT04797442", "access_depth": "abstract_metadata", "consensus_aspect": "Live strain full-population null versus baseline subgroup", "result_comparison": "Consensus separates live WST01 from pasteurized MucT. The original 58-person 12-week trial abstract confirms no overall HbA1c/weight advantage and low-baseline colonization/clinical signals. Baseline abundance is measurable before outcomes, but exploratory subgroup and within-group significance cannot automatically establish a prospective replicated treatment interaction.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/39879980/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\akkermansia-metabolic-health\\examinations\\original-38-46-10000.json" ], "body_receipts": [] }, { "pmid": "40451504", "doi": "10.1016/j.clnesp.2025.05.045", "source_type": "primary study report", "study_group": "PMID40451504", "access_depth": "abstract_metadata", "consensus_aspect": "Yogurt endpoints and untested physical fitness", "result_comparison": "Consensus reports selected postbiotic-yogurt anthropometric benefits and says physical fitness was not altered. The original abstract reports waist, fat, AST and appetite comparisons over eight weeks, without a documented physical-fitness contrast. We preserve its product-specific positive endpoints and treat physical function as not established from the examined record, rather than infer a measured null.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/40451504/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\akkermansia-metabolic-health\\examinations\\original-46-54-10000.json" ], "body_receipts": [] } ], "grade_changed": false, "grade_change_note": "Source-based adjudication; no independent blinded regrade claimed.", "raw_receipts": [ { "path": "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\akkermansia-metabolic-health\\consensus-browser-2026-10-13.json", "sha256": "6fcd4f1a47bdb15df8beb222a435eb74eb982a8f1102456d3d2bc59d0415b48f" } ], "independent_blinded_audit": false, "cutoff": "2026-10-13", "completed_utc": "2026-10-13T17:02:52.660088+00:00", "conclusion": "Endpoint hierarchy, experimental scope and original-source limits determine the evidence cards; provider wording does not override them." } }