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Diabetes Publish Ahead of Print published online ahead of print March 10, 2008
DOI: 10.2337/db07-1403
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Original Research

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

Patrice D. Cani1,,2, Rodrigo Bibiloni3, Claude Knauf2, Aurélie Waget2, Audrey M. Neyrinck1, Nathalie M. Delzenne1, and Rémy Burcelin2

1Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Université catholique de Louvain, Brussels, Belgium
2Rangueil Institute of Molecular Medicine, I2MR, IFR31, Toulouse, France
3 Nestlé Research Center, Department of Nutrition and Health, Lausanne, Switzerland

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, second, that high-fat feeding modulates gut microbiota and the plasma concentration of lipopolysaccharide (LPS) i.e. metabolic endotoxemia. Hence, it remained to demonstrate whether changes in gut microbiota control the occurrence of metabolic diseases.

Objective: first, to demonstrate that changes in gut microbiota, by the mean of antibiotic treatment, 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 ceacal content of LPS in both high-fat fed and ob/ob mice. This effect was correlated with reduced glucose intolerance, body weight gain and fat mass development, lower inflammation, oxidative stress, and macrophages 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 which 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.

Key Words: Diabetes • obesity • gut microbiota • prebiotics • endotoxin • inflammation


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