The Interaction Between Rat Fecal Metabonome And Microbiome During The Preobesity State

Obesity resulting from interactions of genetic and environmental factors becomes a worldwide epidemic and serious public health problem by altering the metabolic phenotypes in multiple biological matrices involving multiple metabolic pathways. High-fat diet (HFD) induced obesity is also accompanied by the imbalance of gut microbiome and metabolic alteration of intestinal bile acids (BAs).To elucidate the change pattern of fecal BAs and the relationship between gut microbiota and fecal BAs during development of obesity, we established an UPLC-MS/MS-based BA-quantitative method and assigned C and H chemical shifts of some bile acids with combination 1H NMR and 2D NMR technique. To understand the contributions of gut microbiota to obesity development and the relationship between gut microbiota and fecal metabolites during development of obesity, we analyzed dynamic alterations of 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 and that different BAs had different change law which was related to their metabolic pathways and physiological function during the dietary intervention. Both the alterations of gut microbiome and fecal BAs profile reached the greatest extent at their middle time points (day 28 or day 56), while the variations were alleviative at the end of experiment, indicating that intestinal microbiome and BAs profile arrived a new homeostasis which meant occurrence of obesity. 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. Robust correlation analysis between dynamic gut microbiome and intestinal BAs profile during development of obesity provided the important information about bacterial BA-metabolized functions, especially for unconfirmed strain which with high content. For instance, deoxycholic acid (DCA) was highly positively correlated with specific strain of Lanchnospiraceae and Roseburia, whereas negatively correlated with unidentified S24-7. These findings offered new sights to assess the contribution of gut microbiome to host metabolism and provided vital information about the effects of gut microbiota on metabolic disorders which might be important for development of obesity prevention and treatments.