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Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity

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Everard, Amandine [UCL] Belzer, Clara Geurts, Lucie [UCL] Ouwerkerk, Janneke P Druart, Céline [UCL] Bindels, Laure B. [UCL] Guiot, Yves [UCL] Muccioli, Giulio [UCL] Delzenne, Nathalie M. [UCL] Cani, Patrice D. [UCL]

Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2013
Language Anglais
Journal information "Proceedings of the National academy of sciences of the United States of America" - Vol. 110, no.22, p. 9066-9071 (2013)
Peer reviewed yes
Publisher National academy of sciences ((United States) Washington, DC)
issn 0027-8424
e-issn 1091-6490
Publication status Publié
Affiliations UCL - (SLuc) Autre
UCL - SSS/LDRI - Louvain Drug Research Institute
UCL - SSS/IREC/MORF - Pôle de Morphologie
UCL - (MGD) Service d'anatomie pathologique
Links
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Bibliographic reference Everard, Amandine ; Belzer, Clara ; Geurts, Lucie ; Ouwerkerk, Janneke P ; Druart, Céline ; et. al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. In: Proceedings of the National academy of sciences of the United States of America, Vol. 110, no.22, p. 9066-9071 (2013)
Permanent URL http://hdl.handle.net/2078.1/131542