Tissue-wide Metabolomics Reveals Wide Impact of Gut Microbiota on Mice Metabolite Composition

Abstract BackgroundThe essential role of gut microbiota in health and disease is well recognized, but the biochemical details that underlie the beneficial impact remain largely undefined. To maintain its stability, microbiota participates in an interactive host-microbiota metabolic signaling, impacting the metabolic phenotypes of the host. Dysbiosis of gut bacteria results in the alteration of certain microbial and host metabolites, and identifying these markers could enhance the early detection of certain diseases. Herein, we report LC-MS based non-targeted metabolic profiling that demonstrates a large effect of gut microbiota on mammalian tissue metabolites. It was hypothesized that gut microbiota influences the overall biochemistry of the host metabolome and this effect is tissue-specific. ResultsThirteen different tissues from germ-free (GF) and conventional (MPF) C57BL/6NTac mice were selected and their metabolic differences were analyzed. Our study demonstrated a large effect of the microbiome on mammalian biochemistry at different tissue levels and resulted in statistically significant modulation of metabolites from multiple metabolic pathway and subpathway classifications (p ≤ 0.05). Hundreds of molecular features were detected exclusively in one mouse group, with the majority of these being unique to specific tissue. A significantly large number of chemical classes were found in the gastrointestinal tissues and arose because of the presence of the microbiome, wherein at least 59% of all detectable features vary in abundance between the two mouse lines. ConclusionsA vast metabolic response of host to metabolites generated by the microbiota was observed, suggesting that the gut microbiota has a direct impact on host metabolism.