title: Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice.
abstract: OBJECTIVE
  Diabetes and obesity are characterized by a low-grade inflammation whose molecular origin is unknown. We previously determined, first, that metabolic endotoxemia controls the inflammatory tone, body weight gain, and diabetes, and second, that high-fat feeding modulates gut microbiota and the plasma concentration of lipopolysaccharide (LPS), i.e., metabolic endotoxemia. Therefore, it remained to demonstrate whether changes in gut microbiota control the occurrence of metabolic diseases.
  
  
  METHODS
  We changed gut microbiota by means of antibiotic treatment to demonstrate, first, that changes in gut microbiota could be responsible for the control of metabolic endotoxemia, the low-grade inflammation, obesity, and type 2 diabetes and, second, to provide some mechanisms responsible for such effect.
  
  
  RESULTS
  We 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. This effect was correlated with reduced glucose intolerance, body weight gain, fat mass development, lower inflammation, oxidative stress, and macrophage infiltration marker mRNA expression in visceral adipose tissue. Importantly, high-fat feeding strongly increased intestinal permeability and reduced the expression of genes coding for proteins of the tight junctions. Furthermore, the absence of CD14 in ob/ob CD14(-)(/)(-) mutant mice mimicked the metabolic and inflammatory effects of antibiotics.
  
  
  CONCLUSIONS
  This new finding demonstrates that changes in gut microbiota controls metabolic endotoxemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability. It would thus be useful to develop strategies for changing gut microbiota to control, intestinal permeability, metabolic endotoxemia, and associated disorders.
authors.affiliation: Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Bibiloni
authors.forename: Claude
authors.initials: C
authors.lastname: Knauf
authors.forename: Aurélie
authors.initials: A
authors.lastname: Waget
authors.forename: Audrey M
authors.initials: AM
authors.lastname: Neyrinck
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Delzenne
authors.forename: Rémy
authors.initials: R
authors.lastname: Burcelin
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001439:Bacteroides / Q000235:genetics / Q000302:isolation & purification; D001483:Base Sequence; D001644:Bifidobacterium / Q000235:genetics / Q000302:isolation & purification; D002432:Cecum / Q000382:microbiology*; D003433:Crosses, Genetic; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D019446:Endotoxemia / Q000503:physiopathology / Q000517:prevention & control*; D005243:Feces / Q000382:microbiology; D005260:Female; D005838:Genotype; D007249:Inflammation / Q000517:prevention & control; D007778:Lactobacillus / Q000235:genetics / Q000302:isolation & purification; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics; D012329:RNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial