For years, researchers studying the gut microbiome observed that people with obesity, type 2 diabetes, and metabolic syndrome tended to have lower levels of a specific bacterium called Akkermansia muciniphila. The correlation appeared in several studies, though a later systematic review found the differences inconsistent across studies, and it prompted a straightforward question [3]: what happens if you give it back to people who have lost it? The 2019 Depommier trial, published in Nature Medicine, was the first human study designed to answer that question in a controlled setting.
Published under the full title ‘Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study,’ this was a small, carefully conducted pilot trial, not a large pivotal study. Its findings attracted significant attention and helped launch the current wave of Akkermansia supplements, but understanding exactly what the trial measured, how large it was, and what its limitations were is essential before drawing conclusions about your own health.
Key Takeaways
- The Depommier 2019 trial was the first human safety and tolerability study of Akkermansia muciniphila supplementation; its primary finding was that both live and pasteurized forms were reported safe and well tolerated over three months in 40 overweight or obese insulin-resistant adults, although EFSA judged the trial of limited value for safety [1][4].
- Pasteurized Akkermansia showed favorable trends in insulin sensitivity, fasting insulinemia, and total cholesterol compared with placebo, though the study was small and these metabolic findings are exploratory [1].
- Only the pasteurized arm improved insulin sensitivity versus placebo, while the live preparation did not significantly improve it. Mouse data on live versus pasteurized forms are mixed, and the pilot did not test which component drives the effect [5][1][6][7][8][9]..
- With 40 participants enrolled across three arms and 32 completing, the trial was too small to confirm cardiometabolic effects; larger replication studies are needed before strong clinical conclusions can be drawn [1][4].
- The results apply specifically to overweight or obese insulin-resistant adults and should not be generalized [1][4] to other populations without additional evidence.
Why Researchers Were Interested in Akkermansia Before This Trial
Akkermansia muciniphila lives in the mucus layer of the intestine and makes up more than 1 percent of the gut microbiome in healthy adults. It degrades mucin, the glycoprotein that lines the gut wall, but rather than harming the barrier, this activity appears to stimulate the host to continuously regenerate it: an interaction that may help maintain tight-junction integrity between intestinal cells.
Animal work had already hinted at metabolic benefits. A 2017 mouse study demonstrated that feeding obese and diabetic mice either a purified outer-membrane protein from Akkermansia called Amuc_1100, or a heat-treated (pasteurized) version of the whole bacterium, improved glucose tolerance and reduced fat-mass gain compared with controls [2]. That study also showed that the pasteurized form retained much of the benefit of the live bacterium: an observation that would directly shape the design of the human trial that followed.
Study Design: Who Was Enrolled and How
The Depommier 2019 trial enrolled 40 overweight or obese insulin-resistant adults, and 32 completed it. It was not a trial defined by metabolic syndrome [1][4]. Participants with active gastrointestinal disease or who were taking medications that could confound the results were excluded.
Research note: The weight change with pasteurized A. muciniphila versus placebo was small and did not reach conventional significance (P = 0.091), so the pilot trial does not show a weight-loss effect [1].
Volunteers were randomized into three groups: a placebo group, a group receiving live Akkermansia muciniphila, and a group receiving pasteurized Akkermansia muciniphila. The supplementation period lasted three months, and neither participants nor assessors knew which group a person had been assigned to for most key endpoints. The primary aim was to establish whether supplementation was safe and well-tolerated: a necessary first step before any larger efficacy trial could be justified [1].
It is important to note the scale. Of the 40 enrolled, 32 completed the trial across three arms. This is appropriate for a proof-of-concept pilot, but EFSA judged the trial of limited value for safety because it was an efficacy study with few subjects, a low dose, a short duration and few safety endpoints [1][4].
Safety and Tolerability: The Primary Finding
The headline result of the Depommier trial was that supplementation with both live and pasteurized Akkermansia appeared to be safe and well-tolerated over three months in these metabolically compromised volunteers [1]. No serious adverse events were attributed to the supplement, and no meaningful changes in safety blood panels were observed. EFSA later judged the trial of limited value for safety, because it was an efficacy study with few subjects, a low dose, a short duration and few safety endpoints [4].
The safety finding matters because Akkermansia is a gram-negative bacterium, meaning it carries lipopolysaccharide (LPS) in its outer membrane. LPS is a potent pro-inflammatory molecule, and there was a legitimate theoretical concern that supplementing with a gram-negative organism could worsen systemic inflammation, particularly in people who already have some degree of gut barrier dysfunction. The trial data did not support that concern, at least over a three-month period in this population [1].
Metabolic Outcomes: What Improved and in Which Group
Beyond safety, the researchers measured a range of cardiometabolic markers. Participants who received pasteurized Akkermansia showed improvements in insulin sensitivity and reductions in fasting insulinemia compared with the placebo group [1]. Plasma total cholesterol also declined in the pasteurized group. These are clinically meaningful markers given the population enrolled, though again the sample size means these findings are exploratory rather than confirmatory.
In the first human pilot, insulin sensitivity improved with the pasteurized form but the weight change was not statistically significant
Improved: +28.62%
Pasteurized Akkermansia versus placebo (P = 0.002) in overweight or obese insulin-resistant adults. 40 were enrolled and 32 completed.
No significant improvement
The live preparation did not significantly improve insulin sensitivity in the same pilot. The trial was not designed to compare the two active forms head to head.
Not significant
Weight slightly decreased by 2.27 kg with the pasteurized form versus placebo (P = 0.091), which did not reach conventional significance.
The pilot supports a signal for insulin sensitivity with the pasteurized form, not for weight loss.
Randomized, double-blind, placebo-controlled pilot. Small sample; larger trials have not repeated the insulin result. Source: Depommier et al., Nature medicine 2019
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One of the more striking observations was that only the pasteurized arm improved insulin sensitivity versus placebo, while the live preparation did not significantly improve it. Earlier mouse data on live versus pasteurized forms are mixed, with some work favoring pasteurized cells and one study finding that viable cells were needed, so the pilot does not show which component drives the effect. Oxygen sensitivity of the live bacterium is the stated reason researchers have suggested inactive forms [5][6][7][8].
After supplementation the overall gut microbiome structure was unaffected, while blood markers of liver dysfunction and inflammation were reduced [1]. No verified fact here shows the trial demonstrated a gut barrier effect, so this should not be read as support for reinforced intestinal barrier function [1].
The Amuc_1100 Protein: A Proposed Mechanism
A key thread connecting the 2017 mouse work and the 2019 human trial is the outer-membrane protein Amuc_1100. In mouse models, this protein interacted with Toll-like receptor 2 on intestinal cells, triggering downstream signaling that improved gut barrier function and metabolic parameters even without the presence of live bacteria [2]. In mice, Amuc_1100 withstands pasteurization temperatures, but the human pilot did not test whether this explains why only the pasteurized arm improved [2][5].
Whether this same protein-receptor interaction drives the metabolic improvements seen in the 2019 human trial is plausible but not fully established. The human trial was not designed to isolate the contribution of Amuc_1100 specifically; it tested whole preparations, not purified proteins. The mechanistic link from mouse data to human outcomes remains an active area of investigation rather than a settled fact [1].
What This Trial Does Not Tell Us
The Depommier 2019 trial is genuinely important: it established human safety data and provided early signals that metabolic benefits seen in animals might translate to people. But it has clear boundaries. With 32 completers across three arms, most of the metabolic findings are exploratory [1] and require replication in larger, adequately powered trials before they can be treated as confirmed effects [1].
The study enrolled a specific population: overweight or obese insulin-resistant adults [1][4]. The results cannot be straightforwardly generalized to healthy adults with normal metabolic profiles, older populations, people with different disease states, or individuals already taking medications that affect the gut microbiome. The trial also ran for three months; longer-term safety and efficacy data are not available from this study.
The trial also does not tell us what dose is optimal, whether effects persist after stopping supplementation, how Akkermansia interacts with specific dietary patterns, or how supplementation compares with lifestyle interventions that naturally raise Akkermansia abundance, such as increased dietary fiber intake or time-restricted eating.
Later trials add context. A 2026 placebo-controlled trial in 142 adults with metabolic syndrome, using 30 billion pasteurized cells daily, did not meet its primary endpoint of whole-body insulin sensitivity, and its authors include employees and a co-founder of the maker. A separate 2026 trial in 90 adults after a low-energy diet found less weight regain with pasteurized MucT than with placebo [10][11][5].
🛒 Where to Buy Akkermansia muciniphila
- Pendulum Akkermansia
delayed-release capsules, 100M AFU: Live A. muciniphila strain (WB-STR-0001); single-strain with chicory inulin, third-party tested. - Codeage Akkermansia Muciniphila
capsules, 100M AFU, 90 ct: Lower-cost Akkermansia plus chicory inulin synbiotic; 3-month supply, gluten-free. - Double Wood Akkermansia Probiotic + Postbiotic
capsules, per label: Budget Akkermansia option marketed around GLP-1 and postbiotic support.
As an Amazon Associate we earn from qualifying purchases. Akkermansia is a live, oxygen-sensitive strain: choose a delayed-release, third-party-tested product with a stated live AFU count.
A Note on the Evidence
Akkermansia muciniphila supplements are not FDA-approved to treat, cure, or prevent any disease, and the human evidence base now includes several small or manufacturer-linked trials of pasteurized Akkermansia, with mixed results, beyond this 2019 proof-of-concept pilot in insulin-resistant adults [1][10][11][12]. Individuals who are immunocompromised, taking immunosuppressive medications, pregnant, or living with active inflammatory bowel disease should consult a qualified healthcare provider before use; this article is informational only and does not constitute medical advice.
Frequently Asked Questions
What was the main purpose of the Depommier 2019 trial?
The study was a proof-of-concept exploratory trial designed primarily to determine whether supplementing with Akkermansia muciniphila was safe and tolerable in overweight or obese insulin-resistant adults. Secondary endpoints included metabolic markers. The authors characterized it as hypothesis-generating rather than confirmatory [1][4].
How many people were in the study?
Forty participants were enrolled and randomized across three groups: placebo, live Akkermansia, and pasteurized Akkermansia, and 32 of them completed the trial. That is appropriate for a safety pilot but too small to reliably confirm effects on metabolic outcomes [1][4].
Did pasteurized Akkermansia work better than the live form?
Only the pasteurized arm improved insulin sensitivity versus placebo, while the live preparation did not significantly improve it, and the trial was not designed to statistically compare the two active groups against each other [1]. Mouse data on live versus pasteurized forms are mixed, so which component drives the effect is not established [5][1][6][7][8].
Did the study show that Akkermansia improves gut barrier function?
No verified fact shows that the trial demonstrated a gut barrier effect. After supplementation the overall gut microbiome structure was unaffected, while blood markers of liver dysfunction and inflammation were reduced [1].
Is the Depommier trial enough evidence to conclude Akkermansia supplements work?
Not on its own. The 2019 trial was an important first step, it established safety signals and provided early metabolic data in humans, but proof-of-concept trials with small sample sizes are the beginning of an evidence chain, not the end. Larger, adequately powered randomized controlled trials are needed to confirm whether the observed trends represent real, reproducible effects [1].
Who should be cautious about taking Akkermansia supplements?
The 2019 trial excluded people with active gastrointestinal disease. More broadly, Akkermansia is a live or pasteurized bacterial preparation, and live probiotic formulations may carry risk for immunocompromised individuals, those on immunosuppressive therapy, or persons with active inflammatory bowel disease. Anyone in these groups, or anyone with significant health conditions, should consult a physician before starting any probiotic supplement [1].
References
- Depommier C et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nature medicine (2019). PMID 31263284
- Plovier H et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nature medicine (2017). PMID 27892954
- Letchumanan G et al. Gut Microbiota Composition in Prediabetes and Newly Diagnosed Type 2 Diabetes: A Systematic Review of Observational Studies. Frontiers in cellular and infection microbiology (2022). PMID 36046745
- European Food Safety Authority (NDA Panel) Safety of pasteurised Akkermansia muciniphila as a novel food pursuant to Regulation (EU) 2015/2283. European Food Safety Authority (NDA Panel) (2021). source
- Liu Y et al. Pasteurized Akkermansia muciniphila as a candidate multi-effector pharmacological system in the gut-liver axis: evidence, unresolved causality, and translational priorities. Frontiers in pharmacology (2026). PMID 42846334
- Fatemeh Ashrafian et al. Comparative effects of alive and pasteurized Akkermansia muciniphila on normal diet-fed mice. Scientific Reports (2021). PMID 34504116
- Fatemeh Ashrafian et al. Extracellular vesicles and pasteurized cells derived from Akkermansia muciniphila protect against high-fat induced obesity in mice. Microbial Cell Factories (2021). PMID 34863163
- Amandine Everard et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proceedings of the National Academy of Sciences (2013). PMID 23671105
- Jiaxiu Liu et al. Live and pasteurized Akkermansia muciniphila decrease susceptibility to Salmonella Typhimurium infection in mice. Journal of Advanced Research (2023). PMID 36996967
- Suenaert P 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). PMID 42343233
- Mount S et al. Pasteurized Akkermansia muciniphila MucT for weight loss maintenance in people with overweight and obesity: a controlled randomized trial. Nature medicine (2026). PMID 42120725
- Kang CH et al. Pasteurized Akkermansia muciniphila HB05 (HB05P) Improves Muscle Strength and Function: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients (2024). PMID 39683431
These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease. Content is for informational purposes only and is not medical advice; consult a qualified healthcare provider before starting any supplement. As an Amazon Associate we earn from qualifying purchases.
