Novel metabolome and breath platforms to trace microbiome contribution to host metabolism

Abstract

Host diet influences the structure and function of the microbiota in species that regularly consume food. To measure the functional contribution of microbiotas, we developed a metabolome‐microbiome platform (MMP) and novel stable isotopic labeling to trace microbiotas' metabolism in breath, cecum, and host tissues. We combined cavity ringdown spectroscopy to measure real‐time breath biomarkers and NMR‐based metabolomics to analyze metabolome profiles in tissues. We applied MMP to hibernating ground squirrels to assess the role of bacterial metabolism contributing to seasonal changes in diet. Previously, we showed that the long‐term fast of hibernation decreases relative abundance of bacterial taxa that are adept at degrading abundant plant glycans in summer versus their reduction in winter. Here, we determined the functional significance of seasonally changing microbiotas by gavaging Spring and Summer squirrels and aroused hibernators in Winter with 13C‐labeled complex and simple carbohydrates, and comparing against their respective intraperitoneal and antibiotics applications. Measurement of 13CO2/12CO2(δ13C) in breath was used as an index of bacterial degradation of 13C‐substrates and linked to observed changes in 1H‐[13C]‐metabolome profiles. Compared with robust responses in Summer changes in δ13C after 13C‐inulin gavage in hibernators were nearly abolished, whereas squirrels in Early Winter and Spring showed variable responses consistent with their transitional microbiotas. Metabolome profiles mirrored seasonal changes in 13C‐labeled short‐chain fatty acids. These suggest that during hibernation, the gut microbiota gradually loses the capacity to degrade a plant‐derived glycan, and a shift away from taxa that prefer dietary substrates. The results suggest MMP is a powerful tool in analysis of host‐microbe relationships.Support or Funding InformationSupported by funds from NSF (IOS1558044), UW‐Madison Graduate and Veterinary Medicine.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.