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United States Department of Agriculture

Agricultural Research Service

Research Project: MOLECULAR, CELLULAR, AND REGULATORY ASPECTS OF OBESITY DEVELOPMENT IN CHILDREN

Location: Children's Nutrition Research Center

Title: Colonic mucosal DNA methylation, immune response, and microbiome patterns in Toll-like receptor 2-knockout mice

Authors
item Kellermayer, Richard -
item Dowd, Scot -
item Harris, Alan -
item Balasa, Alfred -
item Schaible, Tiffany -
item Wolcott, Randy -
item Tatevian, Nina -
item Szigeti, Reka -
item Li, Zhijie -
item Versalovic, James -
item Smith, Wayne -

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 1, 2011
Publication Date: May 1, 2011
Citation: Kellermayer, R., Dowd, S.E., Harris, A.R., Balasa, A., Schaible, T.D., Wolcott, R.D., Tatevian, N., Szigeti, R., Li, Z., Versalovic, J., Smith, W.C. 2011. Colonic mucosal DNA methylation, immune response, and microbiome patterns in Toll-like receptor 2-knockout mice. Federation of American Societies for Experimental Biology Conference. 25: 1449-1460.

Interpretive Summary: This study is an extension of our earlier work on a role for TLR2 in the inflammation that results from diet-induced obesity. TLR2 is a member of the family of cell surface proteins that recognize products released by bacteria as well as saturated fatty acids. We sought to determine the consequences of TLR2 deficiency on gene expression and intestinal microorganisms. There is now evidence that the organisms in the gastrointestinal track may influence diet-induced inflammation. The results show that the expression of genes involved in inflammation was significantly modified by the absence of TLR2 and several gut bacterial species were significantly different in abundance between WT and TLR2-deficient animals. Thus, understanding diet-induced obesity must consider changes in gene expression in the colonic mucosa and the balance of microorganisms within the intestines.

Technical Abstract: The stunning complexity of the resident microbiota and the intricate pathways of microbial and host interactions provide a massive adaptive capacity for mammals. In this addendum we reflect on our recent publication on Toll-like receptor 2 deficiency related colonic mucosal epigenetic, immunologic and microbiomic changes. Our findings underscored the tremendous flexibility of the gut and its microbiota. This flexibility can provide means to overcome significant environmental or genetic challenges. In the meantime, the challenged intestinal system may become vulnerable to otherwise tolerable insults. In such instances, the fine-tuned mutualistic balance between the gut and its microflora may collapse leading to dysbiosis and disease. The ultimate challenge for biomedical research in these cases is to find optimal means for the restoration and maintenance of healthy host physiology.

Last Modified: 10/1/2014
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