Abstract

Understanding the Impact of Tempol on the Gut Microbiome through Next Generation Sequencing and Metabolomics

Andrew Patterson, Assistant Professor, Penn State University

The anti-oxidant tempol reduces obesity in high-fat diet (HFD)-fed mice, but the mechanism for this effect has remained elusive. A mass spectrometry-based metabolomic investigation revealed that tempol altered levels of suspected gut microbe-generated metabolites, thus providing initial clues that tempol may either change the composition of the gut microbiome and/or alter its metabolic potential. Indeed, metagenomics revealed that tempol altered the gut microbiome by preferentially reducing the genus Lactobacillus and its bile salt hydrolase activity leading to the accumulation of intestinal tauro-beta-muricholic acid (TßMCA), a farnesoid X receptor (FXR) antagonist involved in the regulation of bile acid, lipid and glucose metabolism. Using a combination of next generation RNA sequencing, 1H NMR-, and mass spectrometry-based metabolomics, tempol was found to significantly alter the gut microbiome in terms of its metabolic potential (RNAseq) and metabolism (metabolomics). Current work using genetically-modified and germ free mice to distinguish the host from the microbiome response will be presented.