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

Overview
Journal Science
Specialty Science
Date 2010 Mar 6
PMID 20203013
Citations 978
Authors
Matam Vijay-Kumar
Jesse D Aitken
Frederic A Carvalho
Tyler C Cullender
Simon Mwangi
Shanthi Srinivasan
Shanthi V Sitaraman
Rob Knight
Ruth E Ley
Andrew T Gewirtz
Affiliations
Soon will be listed here.
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.

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References
1.
Vijay-Kumar M, Sanders C, Taylor R, Kumar A, Aitken J, Sitaraman S . Deletion of TLR5 results in spontaneous colitis in mice. J Clin Invest. 2007; 117(12):3909-21. PMC: 2075480. DOI: 10.1172/JCI33084. View
2.
Backhed F, Ding H, Wang T, Hooper L, Koh G, Nagy A . The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004; 101(44):15718-23. PMC: 524219. DOI: 10.1073/pnas.0407076101. View
3.
Garrett W, Lord G, Punit S, Lugo-Villarino G, Mazmanian S, Ito S . Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell. 2007; 131(1):33-45. PMC: 2169385. DOI: 10.1016/j.cell.2007.08.017. View
4.
Ley R, Backhed F, Turnbaugh P, Lozupone C, Knight R, Gordon J . Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A. 2005; 102(31):11070-5. PMC: 1176910. DOI: 10.1073/pnas.0504978102. View
5.
Turnbaugh P, Ley R, Mahowald M, Magrini V, Mardis E, Gordon J . An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006; 444(7122):1027-31. DOI: 10.1038/nature05414. View