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-LincolnFollow
• Min Zhang, University of Nebraska-Lincoln
• Phaik Lyn Oh, University of Nebraska-Lincoln
• Derrick Nehrenberg, University of North Carolina
• Kunjie Huab, 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-LincolnFollow
• Daniel Pomp, University of North Carolina

ORCID IDs

Kachman 0000-0003-0506-513X

Walter 0000-0003-1754-172X

Document Type

Article

Date of this Version

2010

Citation

Proceedings of the National Academy of Sciences USA (2010)

doi: 10.1073/pnas.1007028107

Comments

Copyright 2010, National Academy of Sciences USA. 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.