Vitamin D receptor promotes healthy microbial metabolites and microbiome
Abstract
Microbiota derived metabolites act as chemical messengers that elicit a profound impact on host physiology. Vitamin D receptor (VDR) is a key genetic factor for shaping the host microbiome. However, it remains unclear how microbial metabolites are altered in the absence of VDR. We investigated metabolites from mice with tissue-specific deletion of VDR in intestinal epithelial cells or myeloid cells. Conditional VDR deletion severely changed metabolites specifically produced from carbohydrate, protein, lipid, and bile acid metabolism. Eighty-four out of 765 biochemicals were significantly altered due to the Vdr status, and 530 significant changes were due to the high-fat diet intervention. The impact of diet was more prominent due to loss of VDR as indicated by the differences in metabolites generated from energy expenditure, tri-carboxylic acid cycle, tocopherol, polyamine metabolism, and bile acids. The effect of HFD was more pronounced in female mice after VDR deletion. Interestingly, the expression levels of farnesoid X receptor in liver and intestine were significantly increased after intestinal epithelial VDR deletion and were further increased by the high-fat diet. Our study highlights the gender differences, tissue specificity, and potential gut-liver-microbiome axis mediated by VDR that might trigger downstream metabolic disorders.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 30, 2020
- Source ID
- 10.1038/s41598-020-64226-7
Entities
People
- Ishita Chatterjee
- Jilei Zhang
- Jun Sun
- Rong Lu
- Yang Dai
- Yinglin Xia
- Yongguo Zhang
Organizations
- Foundation for the National Institutes of Health
- United States Department of Defense