The Gut Metagenome Across Health and Evolution

The gut microbiome is a contributing factor in animal health. Additionally, perturbations to the gut microbiome can develop into pathological conditions and diseases, presumably because the animal host depends on the metabolic functions of the gut microbiome to maintain homeostasis. Unfortunately, the precise mechanisms through which the gut microbiome operates to influence animal physiology and health remain elusive, which consequently challenges the development of disease diagnostics and therapeutics. We recently conducted a series of comparative microbiomic investigations to uncover potential metabolic mechanisms through which the gut microbiome interacts with its animal host to influence to health. First, we analyzed over 2,000 gut metagenomes from a variety of human clinical populations to statistically model how the metabolic pathways encoded in the microbiome associate with health. This analysis revealed aspects of microbiome metabolism that are perturbed in diseased humans, many of which are common to multiple types of diseases. Second, we compared microbiome samples spanning a diverse evolutionary set of vertebrates to quantify how the microbiome may have diversified over evolutionary timescales. Our analysis reveals properties of the microbiome that are relatively conserved across host species, which indicates that they may have been anciently integrated into the gut microbiome and subsequently retained, potentially because they promote host fitness. Collectively, these investigations clarify the aspects of the gut microbiome that may yield disease when perturbed and implicate their potential interaction with host physiology.