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

Authors

Andrew K. Benson, University of Nebraska-LincolnFollow
Scott A. Kelly, University of North Carolina
Ryan Legge, University of Nebraska-Lincoln
Fangrui Ma, University of Nebraska-LincolnFollow
Soo Jen Low, University of Nebraska-Lincoln
Jaehyoung Kim, University of Nebraska-Lincoln
Min Zhang, University of Nebraska-Lincoln
Phaik Lyn Oh, University of Nebraska-Lincoln
Derrick Nehrenberg, University of North Carolina
Kunjie Hua, University of North Carolina
Stephen D. Kachman, University of Nebraska-LincolnFollow
Etsuko N. Moriyama, University of Nebraska-LincolnFollow
Jens Walter, University of Nebraska-LincolnFollow
Daniel A. Peterson, University of Nebraska-Lincoln
Daniel Pomp, University of North Carolina

ORCID IDs

Stephen D. Kachman

Document Type

Article

Date of this Version

2010

Comments

Published in PNAS, November 2, 2010, vol. 107, no. 44, 18933–18938. Used by Permission.

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 genomewide 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.