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

被引:1656
作者
Plovier, Hubert [1 ]
Everard, Amandine [1 ]
Druart, Celine [1 ]
Depommier, Clara [1 ]
Van Hul, Matthias [1 ]
Geurts, Lucie [1 ]
Chilloux, Julien [2 ]
Ottman, Noora [3 ,7 ]
Duparc, Thibaut [4 ]
Lichtenstein, Laeticia [4 ]
Myridakis, Antonis [2 ]
Delzenne, Nathalie M. [1 ]
Klievink, Judith [5 ]
Bhattacharjee, Arnab [5 ]
van der Ark, Kees C. H. [3 ]
Aalvink, Steven [3 ]
Martinez, Laurent O. [4 ]
Dumas, Marc-Emmanuel [2 ]
Maiter, Dominique [6 ]
Loumaye, Audrey [6 ]
Hermans, Michel P. [6 ]
Thissen, Jean-Paul
Belzer, Clara [3 ]
de Vos, Willem M. [3 ,5 ]
Cani, Patrice D. [1 ]
机构
[1] Catholic Univ Louvain, Louvain Drug Res Inst, WELBIO Walloon Excellence Life Sci & Blotechnol, Metab & Nutr Res Grp, Brussels, Belgium
[2] Imperial Coll, Dept Surg & Canc, Div Computat & Syst Med, London, England
[3] Wageningen Univ, Microbiol Lab, NL-6700 AP Wageningen, Netherlands
[4] INSERM, Inst Metab & Cardiovasc Dis, I2MC, UMR 1048, Toulouse, France
[5] Univ Helsinki, Dept Bacteriol & Immunol, RPU Immunobiol, Helsinki, Finland
[6] Catholic Univ Louvain, Clin Univ St Luc, Inst Rech Expt & Clin IREC, Pole Endocrinol Diabet & Nutr, Brussels, Belgium
[7] Univ Helsinki, Metapopulat Res Ctr, Helsinki, Finland
基金
芬兰科学院; 欧洲研究理事会;
关键词
GUT MICROBIOTA; INTESTINAL EPITHELIUM; INSULIN-RESISTANCE; ATHEROSCLEROSIS; SAFETY; MUCIN; TOLERANCE; DIET; INFLAMMATION; INTEGRITY;
D O I
10.1038/nm.4236
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:107 / 113
页数:7
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