Host genetic variation affecting the microbiome in rhesus macaques

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PROJECT SUMMARY An increasing body of literature has focused on associating the microbiome with human diseases including obesity, type II diabetes, cardiovascular disease, cancers, and psychiatric disorders such as autism, schizophrenia, and depression. While these associations are still relatively nascent and largely correlative, it has not stopped the push towards development of therapeutics aimed at manipulating the microbiome in an effort to treat these disorders. There remain, however, a great deal of unknowns surrounding the microbiome ranging from the factors responsible for its composition to the nature and sources of inter-individual variability to the actual causative links between microbiome and disease, particularly in humans. This is complicated by differences in physiology and microbiome composition between humans and rodent models and the pervasive effects of the environment that cannot be controlled for in humans. This proposal uses 1300 rhesus macaques from 4 colonies to investigate variability in the gastrointestinal, oral, and nasal microbiome. It will characterize the inter-individual variability that exists across animals and further develop the rhesus macaque as a model for human microbiome studies. Leveraging 800 animals with whole genome sequence available and 500 animals with whole exome sequence available, we also propose genome-wide and exome-wide association studies on measures of microbiome diversity and specific bacterial taxa. This data can then be used to complement and focus human genetic studies of the microbiome. This will not only further our understanding of factors that affect microbiome composition, but it will also assist in the development of primate models for testing disease associations with the microbiome and for testing the ability of therapeutic interventions to alter the microbiome.