1: Diabetes. 2008 Jun;57(6):1470-81. Epub 2008 Feb 27.

Changes in gut microbiota control metabolic endotoxemia-induced inflammation in
high-fat diet-induced obesity and diabetes in mice.

Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R.

Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Université
catholique de Louvain, Brussels, Belgium.

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. RESEARCH DESIGN AND 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.


PMID: 18305141 [PubMed - in process]

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