Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity
Amandine Everard,Clara Belzer,Lucie Geurts,Janneke P. Ouwerkerk,Céline Druart,Laure B. Bindels,Yves Guiot,Muriel Derrien,Giulio G. Muccioli,Nathalie M. Delzenne,Willem M. de Vos,Willem M. de Vos,Patrice D. Cani +12 more
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TLDR
Substantial insight is provided into the intricate mechanisms of bacterial regulation of the cross-talk between the host and gut microbiota and provides 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.Abstract:
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.read more
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Metabolic endotoxemia initiates obesity and insulin resistance
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TL;DR: It is concluded that the LPS/CD14 system sets the tone of insulin sensitivity and the onset of diabetes and obesity and lowering plasma LPS concentration could be a potent strategy for the control of metabolic diseases.
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A metagenome-wide association study of gut microbiota in type 2 diabetes
Junjie Qin,Yingrui Li,Zhiming Cai,Shenghui Li,Jianfeng Zhu,Fan Zhang,Suisha Liang,Wenwei Zhang,Yuanlin Guan,Dongqian Shen,Yangqing Peng,Dongya Zhang,Zhuye Jie,Wenxian Wu,Youwen Qin,Wenbin Xue,Junhua Li,Lingchuan Han,Donghui Lu,Peixian Wu,Yali Dai,Xiaojuan Sun,Zesong Li,Aifa Tang,Shilong Zhong,Xiaoping Li,Weineng Chen,Ran Xu,Mingbang Wang,Qiang Feng,Meihua Gong,Jing Yu,Yanyan Zhang,Ming Zhang,Torben Hansen,Gaston Sanchez,Jeroen Raes,Gwen Falony,Shujiro Okuda,Mathieu Almeida,Emmanuelle Le-chatelier,Pierre Renault,Nicolas Pons,Jean-Michel Batto,Zhaoxi Zhang,Hua Chen,Ruifu Yang,Wei-Mou Zheng,Songgang Li,Huanming Yang,Jian Wang,S. Dusko Ehrlich,Rasmus Nielsen,Oluf Pedersen,Oluf Pedersen,Karsten Kristiansen,Jun Wang +56 more
TL;DR: MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance.
Journal ArticleDOI
Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice
Patrice D. Cani,Rodrigo Bibiloni,Claude Knauf,Aurélie Waget,Audrey M. Neyrinck,Nathalie M. Delzenne,Rémy Burcelin +6 more
TL;DR: It is found that changes of gut microbiota induced by an antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS in both high-fat–fed and ob/ob mice, demonstrating that changes in gut microbiota controls metabolic endotoxinemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability.
Journal ArticleDOI
Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome
TL;DR: This study illustrates how combining comparative metagenomics with gnotobiotic mouse models and specific dietary manipulations can disclose the niches of previously uncharacterized members of the gut microbiota.
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