Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study.
Level 2 - randomized trial
Individual randomized controlled trial in humans
PubMed 31263284 · doi:10.1038/s41591-019-0495-2
What was done
A randomized, double-blind, placebo-controlled, single-center pilot trial evaluated daily oral supplementation with 10^10 Akkermansia muciniphila (either live or pasteurized) versus placebo for 3 months in 40 overweight or obese insulin-resistant human volunteers (32 completed the trial). Primary endpoints were safety, tolerability, and metabolic parameters (insulin resistance, circulating lipids, visceral adiposity, and body mass). Secondary outcomes were gut barrier function (plasma lipopolysaccharides) and gut microbiota composition.
What was found
Oral supplementation was safe and well tolerated. Compared with placebo, pasteurized A. muciniphila significantly improved insulin sensitivity (+28.62 ± 7.02%, P = 0.002), reduced insulinemia (-34.08 ± 7.12%, P = 0.006), and decreased plasma total cholesterol (-8.68 ± 2.38%, P = 0.02). Reductions in body weight (-2.27 ± 0.92 kg, P = 0.091 vs. placebo), fat mass (-1.37 ± 0.82 kg, P = 0.092 vs. baseline), and hip circumference (-2.63 ± 1.14 cm, P = 0.091 vs. baseline) did not reach statistical significance. A. muciniphila reduced blood markers for liver dysfunction and inflammation, while the overall gut microbiome structure remained unaffected.
Why it matters
This first-in-human proof-of-concept trial establishes that oral pasteurized A. muciniphila is safe and can meaningfully improve insulin sensitivity and cholesterol in overweight and obese insulin-resistant adults.
Limits
Small sample size (40 enrolled, 32 completed), single-center setting, and short duration (3 months). Anthropometric improvements did not reach statistical significance, and numerical results in the abstract are reported primarily for pasteurized bacteria.
Cited by
- supports Dead, pasteurized Akkermansia muciniphila organisms provide significant metabolic benefits comparable to viable bacteria due to surface signaling molecules.