Correlations of Fecal Metabonomic and Microbiomic Changes Induced by High-fat Diet in the Pre-Obesity State

Obesity resulting from interactions of genetic and environmental factors becomes a serious public health problem worldwide with alterations of the metabolic phenotypes in multiple biological matrices involving multiple metabolic pathways. To understand the contributions of gut microbiota to obesity development, we analyzed dynamic alterations in fecal metabonomic phenotype using NMR and fecal microorganism composition in rats using pyrosequencing technology during the high-fat diet (HFD) feeding for 81 days (pre-obesity state). Integrated analysis of these two phenotypic datasets was further conducted to establish correlations between the altered rat fecal metabonome and gut microbiome. We found that one-week HFD feeding already caused significant changes in rat fecal metabonome and such changes sustained throughout 81-days feeding with the host and gut microbiota co-metabolites clearly featured. We also found that HFD caused outstanding decreases in most fecal metabolites implying enhancement of gut absorptions. We further established comprehensive correlations between the HFD-induced changes in fecal metabonome and fecal microbial composition indicating contributions of gut microbiota in pathogenesis and progression of the HFD-induced obesity. These findings provided essential information about the functions of gut microbiota in pathogenesis of metabolic disorders which could be potentially important for developing obesity prevention and treatment therapies.