A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice.
Hubert PlovierAmandine EverardCéline DruartClara DepommierMatthias Van HulLucie GeurtsJulien ChillouxNoora OttmanThibaut DuparcLaeticia LichtensteinAntonis MyridakisNathalie M DelzenneJudith KlievinkArnab BhattacharjeeKees C H van der ArkSteven AalvinkLaurent O MartinezMarc Emmanuel DumasDominique MaiterAudrey LoumayeMichel P HermansJean-Paul ThissenClara BelzerWillem Meindert de VosPatrice D CaniPublished in: Nature medicine (2016)
Obesity and type 2 diabetes are associated with low-grade inflammation and specific changes in gut microbiota composition. We previously demonstrated that administration of Akkermansia muciniphila to mice prevents the development of obesity and associated complications. However, the underlying mechanisms of this protective effect remain unclear. Moreover, the sensitivity of A. muciniphila to oxygen and the presence of animal-derived compounds in its growth medium currently limit the development of translational approaches for human medicine. We have addressed these issues here by showing that A. muciniphila retains its efficacy when grown on a synthetic medium compatible with human administration. Unexpectedly, we discovered that pasteurization of A. muciniphila enhanced its capacity to reduce fat mass development, insulin resistance and dyslipidemia in mice. These improvements were notably associated with a modulation of the host urinary metabolomics profile and intestinal energy absorption. We demonstrated that Amuc_1100, a specific protein isolated from the outer membrane of A. muciniphila, interacts with Toll-like receptor 2, is stable at temperatures used for pasteurization, improves the gut barrier and partly recapitulates the beneficial effects of the bacterium. Finally, we showed that administration of live or pasteurized A. muciniphila grown on the synthetic medium is safe in humans. These findings provide support for the use of different preparations of A. muciniphila as therapeutic options to target human obesity and associated disorders.
Keyphrases
- insulin resistance
- high fat diet induced
- type diabetes
- metabolic syndrome
- toll like receptor
- endothelial cells
- adipose tissue
- low grade
- weight loss
- induced pluripotent stem cells
- high fat diet
- pluripotent stem cells
- polycystic ovary syndrome
- skeletal muscle
- cardiovascular disease
- nuclear factor
- bariatric surgery
- weight gain
- inflammatory response
- human milk
- mass spectrometry
- oxidative stress
- preterm infants
- body mass index
- mouse model
- low birth weight
- risk factors