Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors

TLDR

Gut microbiota composition varies greatly among individuals, and how environmental and genetic factors combine to shape this diversity remains largely unknown. The study examined how environmental and host genetic factors influence gut microbiota composition in a large mouse intercross population of 645 animals. Quantitative pyrosequencing of 64 core microbial taxa in these mice, followed by linkage analysis with 530 SNP markers, identified 18 host QTL associated with microbial abundances. Genotype contributed to microbiota variation, with 18 QTL affecting individual species, related taxa groups, or pleiotropic effects on distant taxa, demonstrating host genetic control of gut microbiome diversity.

Abstract

In vertebrates, including humans, individuals harbor gut microbial communities whose species composition and relative proportions of dominant microbial groups are tremendously varied. Although external and stochastic factors clearly contribute to the individuality of the microbiota, the fundamental principles dictating how environmental factors and host genetic factors combine to shape this complex ecosystem are largely unknown and require systematic study. Here we examined factors that affect microbiota composition in a large ( n = 645) mouse advanced intercross line originating from a cross between C57BL/6J and an ICR-derived outbred line (HR). Quantitative pyrosequencing of the microbiota defined a core measurable microbiota (CMM) of 64 conserved taxonomic groups that varied quantitatively across most animals in the population. Although some of this variation can be explained by litter and cohort effects, individual host genotype had a measurable contribution. Testing of the CMM abundances for cosegregation with 530 fully informative SNP markers identified 18 host quantitative trait loci (QTL) that show significant or suggestive genome-wide linkage with relative abundances of specific microbial taxa. These QTL affect microbiota composition in three ways; some loci control individual microbial species, some control groups of related taxa, and some have putative pleiotropic effects on groups of distantly related organisms. These data provide clear evidence for the importance of host genetic control in shaping individual microbiome diversity in mammals, a key step toward understanding the factors that govern the assemblages of gut microbiota associated with complex diseases.