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Science 328 (5975): 228-231

Copyright © 2010 by the American Association for the Advancement of Science

Metabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5

Matam Vijay-Kumar,1 Jesse D. Aitken,1 Frederic A. Carvalho,1 Tyler C. Cullender,2 Simon Mwangi,3 Shanthi Srinivasan,3 Shanthi V. Sitaraman,3 Rob Knight,4 Ruth E. Ley,2 Andrew T. Gewirtz1,*

Abstract: Metabolic syndrome is a group of obesity-related metabolic abnormalities that increase an individual’s risk of developing type 2 diabetes and cardiovascular disease. Here, we show that mice genetically deficient in Toll-like receptor 5 (TLR5), a component of the innate immune system that is expressed in the gut mucosa and that helps defend against infection, exhibit hyperphagia and develop hallmark features of metabolic syndrome, including hyperlipidemia, hypertension, insulin resistance, and increased adiposity. These metabolic changes correlated with changes in the composition of the gut microbiota, and transfer of the gut microbiota from TLR5-deficient mice to wild-type germ-free mice conferred many features of metabolic syndrome to the recipients. Food restriction prevented obesity, but not insulin resistance, in the TLR5-deficient mice. These results support the emerging view that the gut microbiota contributes to metabolic disease and suggest that malfunction of the innate immune system may promote the development of metabolic syndrome.

1 Department of Pathology, Emory University, Atlanta, GA 30322, USA.
2 Department of Microbiology, Cornell University, Ithaca, NY 14853, USA.
3 Department of Medicine, Emory University, Atlanta, GA 30322, USA.
4 Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.

* To whom correspondence should be addressed. E-mail: agewirt{at}emory.edu

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