First human trial of Akkermansia muciniphila reports safety and mixed metabolic results

Nature Medicine published the first human trial of a supplement made from the gut bacterium Akkermansia muciniphila on July 1, 2019 (volume 25, pages 1096–1103). The study reported that three months of daily oral doses was safe and well tolerated in overweight and obese volunteers with insulin resistance, and that the pasteurized form of the bacterium improved several metabolic measures compared with placebo ^[2].

What the trial tested

The study was a randomized, double-blind, placebo-controlled pilot conducted at a single center. Forty people enrolled and 32 completed the trial. Participants took 10^10 bacteria daily — either live or pasteurized A. muciniphila — or a placebo for three months ^[2].

The primary endpoints covered safety, tolerability and metabolic parameters, including insulin resistance, circulating lipids, visceral adiposity and body mass. The secondary outcomes were gut barrier function, measured by plasma lipopolysaccharides, and gut microbiota composition ^[2].

The metabolic results

Compared with placebo, pasteurized A. muciniphila improved insulin sensitivity by 28.62% (±7.02; P = 0.002), reduced insulinemia by 34.08% (±7.12; P = 0.006) and lowered plasma total cholesterol by 8.68% (±2.38; P = 0.02) ^[2].

Body weight fell by 2.27 kg (±0.92) compared with the placebo group, but that difference did not reach statistical significance (P = 0.091). Fat mass dropped 1.37 kg (±0.82; P = 0.092) and hip circumference fell 2.63 cm (±1.14; P = 0.091) compared with baseline — also short of statistical significance ^[2].

The published summary of the trial does not report separate metabolic results for the live-bacteria group, and it does not state whether the changes persisted after supplementation stopped ^[2]. The researchers describe the work as a proof-of-concept exploratory study ^[2].

Why it matters for patients

This trial did not test a GLP-1 medication. Semaglutide (Ozempic, Wegovy, Rybelsus), tirzepatide (Mounjaro, Zepbound) and orforglipron (Foundayo) were not part of the study, and the results do not add to or change the evidence on those drugs ^[2].

The findings come from a small pilot: 32 people finished it, and the weight difference between the supplement and placebo was not statistically significant. That means the study does not establish that the bacterium causes weight loss in people ^[2]. The metabolic improvements were measured over three months; longer-term safety and effectiveness have not been reported ^[2].

Earlier human studies cited in the paper found a negative correlation between A. muciniphila abundance in the gut and overweight, obesity, untreated type 2 diabetes or hypertension. Those were correlations — they are not evidence that adding the bacterium treats any of those conditions ^[2].

For people already taking a GLP-1 medication, the trial contains no information about combining the two, and no interaction data has been reported ^[2]. Products sold as Akkermansia supplements were not part of the study. Whether commercial products contain the same bacterial strain, preparation or dose used in the trial has not been reported ^[2].

What happens next

The report does not describe any follow-up trial, regulatory filing or approval timeline for A. muciniphila as a treatment ^[2]. Whether the pasteurized preparation used in the study is available to consumers, and in what form, is not addressed ^[2]. The study's conclusions apply only to the 32 participants who completed three months of supplementation, and no date has been disclosed for results from a larger trial ^[2].