Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet–Induced Obesity and Diabetes in Mice

  1. Patrice D. Cani12,
  2. Rodrigo Bibiloni3,
  3. Claude Knauf2,
  4. Aurélie Waget2,
  5. Audrey M. Neyrinck1,
  6. Nathalie M. Delzenne1 and
  7. Rémy Burcelin2
  1. 1Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Université catholique de Louvain, Brussels, Belgium
  2. 2Rangueil Institute of Molecular Medicine, Toulouse, France
  3. 3Nestlé Research Center, Department of Nutrition and Health, Lausanne, Switzerland
  1. Corresponding author: Prof. Rémy Burcelin, Rangueil Institute of Molecular Medicine, I2MR, IFR31, Toulouse, France. E-mail: burcelin{at}toulouse.inserm.fr

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.

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.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 27 February 2008. DOI: 10.2337/db07-1403.

    Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-1403.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted February 25, 2008.
    • Received October 3, 2007.

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  1. Diabetes vol. 57 no. 6 1470-1481
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