Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study
Clara Depommier, Amandine Everard, Céline Druart, Hubert Plovier, Matthias Van Hul, Sara Vieira-Silva, Gwen Falony, Jeroen Raes, Dominique Maiter, Nathalie M Delzenne, Marie de Barsy, Audrey Loumaye, Michel P Hermans, Jean-Paul Thissen, Willem M de Vos, Patrice D Cani, Clara Depommier, Amandine Everard, Céline Druart, Hubert Plovier, Matthias Van Hul, Sara Vieira-Silva, Gwen Falony, Jeroen Raes, Dominique Maiter, Nathalie M Delzenne, Marie de Barsy, Audrey Loumaye, Michel P Hermans, Jean-Paul Thissen, Willem M de Vos, Patrice D Cani
Abstract
Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well as type 2 diabetes mellitus1. The gut microbiota is a new key contributor involved in the onset of obesity-related disorders2. In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated type 2 diabetes mellitus or hypertension3-8. Since the administration of A. muciniphila has never been investigated in humans, we conducted a randomized, double-blind, placebo-controlled pilot study in overweight/obese insulin-resistant volunteers; 40 were enrolled and 32 completed the trial. The primary end points were safety, tolerability and metabolic parameters (that is, insulin resistance, circulating lipids, visceral adiposity and body mass). Secondary outcomes were gut barrier function (that is, plasma lipopolysaccharides) and gut microbiota composition. In this single-center study, we demonstrated that daily oral supplementation of 1010 A. muciniphila bacteria either live or pasteurized for three months was safe and well tolerated. Compared to placebo, pasteurized A. muciniphila improved insulin sensitivity (+28.62 ± 7.02%, P = 0.002), and reduced insulinemia (-34.08 ± 7.12%, P = 0.006) and plasma total cholesterol (-8.68 ± 2.38%, P = 0.02). Pasteurized A. muciniphila supplementation slightly decreased body weight (-2.27 ± 0.92 kg, P = 0.091) compared to the placebo group, and fat mass (-1.37 ± 0.82 kg, P = 0.092) and hip circumference (-2.63 ± 1.14 cm, P = 0.091) compared to baseline. After three months of supplementation, A. muciniphila reduced the levels of the relevant blood markers for liver dysfunction and inflammation while the overall gut microbiome structure was unaffected. In conclusion, this proof-of-concept study (clinical trial no. NCT02637115 ) shows that the intervention was safe and well tolerated and that supplementation with A. muciniphila improves several metabolic parameters.
Conflict of interest statement
Competing financial interests
A.E., C.D., H.P., P.D.C. and W.M.d.V. are inventors of patent applications (PCT/EP2013/073972; PCT/EP2016/071327, PCT/EP2016/060033 filed in European Patent Office (EP), Australia (AU), Brazil (BR), Canada (CA), China (CN), Eurasian Patent Organization (EA), Israel (IL), India (IN), Hong Kong (HK), Japan (JP), South Korea (KR), Mexico (MX), New Zealand (NZ), and the United States (US)) dealing with the use of A.muciniphila and its components in the context of obesity and related disorders. P.D.C. and W.M.d.V. are co-founders of A-Mansia Biotech SA.
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Source: PubMed