title: Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity.
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.
authors.affiliation: Metabolism and Nutrition Research Group, Walloon Excellence in Life sciences and BIOtechnology (WELBIO), Louvain Drug Research Institute, Université catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: Amandine
authors.initials: A
authors.lastname: Everard
authors.forename: Clara
authors.initials: C
authors.lastname: Belzer
authors.forename: Lucie
authors.initials: L
authors.lastname: Geurts
authors.forename: Janneke P
authors.initials: JP
authors.lastname: Ouwerkerk
authors.forename: Céline
authors.initials: C
authors.lastname: Druart
authors.forename: Laure B
authors.initials: LB
authors.lastname: Bindels
authors.forename: Yves
authors.initials: Y
authors.lastname: Guiot
authors.forename: Muriel
authors.initials: M
authors.lastname: Derrien
authors.forename: Giulio G
authors.initials: GG
authors.lastname: Muccioli
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Delzenne
authors.forename: Willem M
authors.initials: WM
authors.lastname: de Vos
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000382:microbiology*; D063388:Endocannabinoids / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006706:Homeostasis / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D009765:Obesity / Q000382:microbiology* / Q000628:therapy; D009844:Oligosaccharides; D056692:Prebiotics; D060888:Real-Time Polymerase Chain Reaction; D061327:Verrucomicrobia / Q000378:metabolism*
chemical_list: D023181:Antimicrobial Cationic Peptides; D017931:DNA Primers; D063388:Endocannabinoids; D009844:Oligosaccharides; D056692:Prebiotics; C120489:oligofructose
keywords: LPS; Lactobacillus plantarum; RegIIIγ; antimicrobial peptides; gut permeability