Journal
NATURE MEDICINE
Volume 23, Issue 1, Pages 107-113Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.4236
Keywords
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Funding
- FIRST Spin-Off grant from the Walloon Region [1410053]
- ERC [250172, 336452-ENIGMO]
- SIAM Gravity Grant [024.002.002]
- Spinoza Award of the Netherlands Organization for Scientific Research
- Academy of Finland [137389, 141140, 1272870]
- FNRS [J.0084.15, 3.4579.11]
- PDR (Projet de Recherche) [T.0138.14]
- ARC (Action de Recherche Concertee-Communaute francaise de Belgique) [12/17-047]
- FRFS-WELBIO [WELBIO-CR-2012S-02R]
- Funds Baillet Latour
- FIRST Spin-Off grant (FSO) from the Walloon Region, Belgium [1410053]
- FP7 METACARDIS [HEALTH-F4-2012-305312]
- POC ERC grant (European Research Council) [Microbes4U_713547]
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Obesity and type 2 diabetes are associated with low-grade inflammation and specific changes in gut microbiota composition(1-7). We previously demonstrated that administration of Akkermansia muciniphila to mice prevents the development of obesity and associated complications(8). 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(9). 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.
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