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A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice

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Plovier, Hubert [UCL] Everard, Amandine [UCL] Druart, Céline [UCL] Depommier, Clara [UCL] Van Hul, Matthias [UCL] Geurts, Lucie [UCL] Delzenne, Nathalie M. [UCL] Maiter, Dominique [UCL] Loumaye, Audrey [UCL] Hermans, Michel [UCL] Thissen, Jean-Paul [UCL] Cani, Patrice D. [UCL]

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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2017
Language Anglais
Journal information "Nature Medicine" - Vol. 23, no. 1, p. 107-113 (2017)
Peer reviewed yes
Publisher Nature Publishing Group ((United States) New York, NY)
issn 1078-8956
e-issn 1546-170X
Publication status Publié
Affiliations UCL - SSS/LDRI - Louvain Drug Research Institute
UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition
UCL - (SLuc) Service d'endocrinologie et de nutrition
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Bibliographic reference Plovier, Hubert ; Everard, Amandine ; Druart, Céline ; Depommier, Clara ; Van Hul, Matthias ; et. al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. In: Nature Medicine, Vol. 23, no. 1, p. 107-113 (2017)
Permanent URL http://hdl.handle.net/2078.1/178990