{
  "cutoff": "2026-10-13",
  "note": "Selected publication milestones, not an exhaustive history or discovery priority claim.",
  "milestones": [
    {
      "pmid": "23671105",
      "year": "2013",
      "title": "Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity.",
      "doi": "10.1073/pnas.1219451110",
      "url": "https://pubmed.ncbi.nlm.nih.gov/23671105/",
      "interpretation": "Early mouse experiments distinguish viable bacteria from the tested heat-killed preparation."
    },
    {
      "pmid": "26100928",
      "year": "2016",
      "title": "Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology.",
      "doi": "10.1136/gutjnl-2014-308778",
      "url": "https://pubmed.ncbi.nlm.nih.gov/26100928/",
      "interpretation": "Human diet intervention links baseline microbial ecology with response without randomizing bacterial abundance."
    },
    {
      "pmid": "27892954",
      "year": "2017",
      "title": "A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice.",
      "doi": "10.1038/nm.4236",
      "url": "https://pubmed.ncbi.nlm.nih.gov/27892954/",
      "interpretation": "Pasteurized cells and Amuc_1100 provide experimental metabolic/barrier sufficiency in mice."
    },
    {
      "pmid": "29379988",
      "year": "2018",
      "title": "Aberrant intestinal microbiota in individuals with prediabetes.",
      "doi": "10.1007/s00125-018-4550-1",
      "url": "https://pubmed.ncbi.nlm.nih.gov/29379988/",
      "interpretation": "Prediabetes taxon association does not transfer impaired glucose regulation to recipient mice."
    },
    {
      "pmid": "29472701",
      "year": "2018",
      "title": "Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions.",
      "doi": "10.1038/emm.2017.282",
      "url": "https://pubmed.ncbi.nlm.nih.gov/29472701/",
      "interpretation": "Akkermansia vesicles provide experimental barrier and glucose effects in recipient models."
    },
    {
      "pmid": "31263284",
      "year": "2019",
      "title": "Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study.",
      "doi": "10.1038/s41591-019-0495-2",
      "url": "https://pubmed.ncbi.nlm.nih.gov/31263284/",
      "interpretation": "The first human pilot shows insulin/HOMA and cholesterol signals but unchanged clinical glycemia in selected body Results."
    },
    {
      "pmid": "32675291",
      "year": "2020",
      "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.",
      "doi": "10.1136/bmjdrc-2020-001319",
      "url": "https://pubmed.ncbi.nlm.nih.gov/32675291/",
      "interpretation": "A defined multi-strain/inulin formulation has a genuine product-specific glucose-control signal."
    },
    {
      "pmid": "33477821",
      "year": "2021",
      "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.",
      "doi": "10.3390/cells10010185",
      "url": "https://pubmed.ncbi.nlm.nih.gov/33477821/",
      "interpretation": "A shared pilot-trial secondary analysis narrows a proposed lipid mediator without proving necessity."
    },
    {
      "pmid": "33820962",
      "year": "2021",
      "title": "Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice.",
      "doi": "10.1038/s41564-021-00880-5",
      "url": "https://pubmed.ncbi.nlm.nih.gov/33820962/",
      "interpretation": "P9 factor and host-pathway experiments narrow a distinct experimental mechanism."
    },
    {
      "pmid": "34683361",
      "year": "2021",
      "title": "Effects of Live and Pasteurized Forms of Akkermansia from the Human Gut on Obesity and Metabolic Dysregulation.",
      "doi": "10.3390/microorganisms9102039",
      "url": "https://pubmed.ncbi.nlm.nih.gov/34683361/",
      "interpretation": "Direct mouse live/pasteurized comparisons map strain/preparation effects."
    },
    {
      "pmid": "35805168",
      "year": "2022",
      "title": "Identification and Characterization of a Novel Species of Genus Akkermansia with Metabolic Health Effects in a Diet-Induced Obesity Mouse Model.",
      "doi": "10.3390/cells11132084",
      "url": "https://pubmed.ncbi.nlm.nih.gov/35805168/",
      "interpretation": "Another Akkermansia species favors its live form, challenging universal processing superiority."
    },
    {
      "pmid": "39683431",
      "year": "2024",
      "title": "Pasteurized Akkermansia muciniphila HB05 (HB05P) Improves Muscle Strength and Function: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.",
      "doi": "10.3390/nu16234037",
      "url": "https://pubmed.ncbi.nlm.nih.gov/39683431/",
      "interpretation": "A different HB05 product improves selected older-adult torque outcomes while grip remains unchanged."
    },
    {
      "pmid": "39879980",
      "year": "2025",
      "title": "Akkermansia muciniphila supplementation in patients with overweight/obese type 2 diabetes: Efficacy depends on its baseline levels in the gut.",
      "doi": "10.1016/j.cmet.2024.12.010",
      "url": "https://pubmed.ncbi.nlm.nih.gov/39879980/",
      "interpretation": "Live WST01 human trial has a whole-group clinical null with exploratory low-baseline signals."
    },
    {
      "pmid": "40451504",
      "year": "2025",
      "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.",
      "doi": "10.1016/j.clnesp.2025.05.045",
      "url": "https://pubmed.ncbi.nlm.nih.gov/40451504/",
      "interpretation": "A short postbiotic-yogurt trial provides formulation-specific selected anthropometric/liver effects."
    },
    {
      "pmid": "42120725",
      "year": "2026",
      "title": "Pasteurized Akkermansia muciniphila MucT for weight loss maintenance in people with overweight and obesity: a controlled randomized trial.",
      "doi": "10.1038/s41591-026-04394-7",
      "url": "https://pubmed.ncbi.nlm.nih.gov/42120725/",
      "interpretation": "Product-specific randomized maintenance trial shows less regain; this positive becomes explicitly post-discovery supplemental SC5."
    },
    {
      "pmid": "42343233",
      "year": "2026",
      "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.",
      "doi": "10.1080/19490976.2026.2690689",
      "url": "https://pubmed.ncbi.nlm.nih.gov/42343233/",
      "interpretation": "Larger MucT trial has a null primary Matsuda endpoint and exploratory baseline-low marker signals."
    },
    {
      "pmid": "41636295",
      "year": "2026",
      "title": "Efficacy of inulin supplementation in metabolic control and Akkermansia muciniphila levels in subjects with type 1 diabetes: a pilot study.",
      "doi": "10.26355/eurrev_202601_37645",
      "url": "https://pubmed.ncbi.nlm.nih.gov/41636295/",
      "interpretation": "Inulin changes selected outcomes without raising Akkermansia or improving HbA1c/CGM."
    },
    {
      "pmid": "42116498",
      "year": "2026",
      "title": "Timing matters in type 2 diabetes: Early high-Fiber nutrition enhances glycemic control and reshapes gut microbiota.",
      "doi": "10.1016/j.foodres.2026.119257",
      "url": "https://pubmed.ncbi.nlm.nih.gov/42116498/",
      "interpretation": "A high-fiber/energy-restriction intervention changes clinical glycemia and several taxa without isolating one microbial mediator."
    }
  ],
  "gaps": [
    "Prospectively meaningful clinical glycemic/function efficacy of exact pasteurized MucT over at least 12 weeks.",
    "Independent maintenance replication and longer durability after a clearly defined pre-maintenance diet lead-in.",
    "Prespecified baseline-low interactions with multiplicity control rather than within-subgroup significance comparisons.",
    "Direct strain/preparation and commercial-product identity comparisons; named mixture success is not component necessity.",
    "Necessary human factor/barrier mediator testing, distinct from purified factor sufficiency in mice.",
    "Complete body/supplement review and long-term safety beyond small short trial populations."
  ],
  "decisive_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."
}