Host genetics and diet, but not immunoglobulin A expression, converge to shape compositional features of the gut microbiome in an advanced intercross population of mice

Authors

Larry J. Leamy, University of North Carolina at CharlotteFollow
Scott A. Kelly, Ohio Wesleyan University
Joseph Nietfeldt, University of Nebraska-LincolnFollow
Ryan M. Legge, University of Nebraska-LincolnFollow
Fangrui Ma, University of Nebraska-LincolnFollow
Kunjie Hua, University of North Carolina at Chapel Hill
Rohita Sinha, University of Nebraska-LincolnFollow
Daniel A. Peterson, Johns Hopkins UniversityFollow
Jens Walter, University of Nebraska-LincolnFollow
Andrew K. Benson, University of Nebraska-LincolnFollow
Daniel Pomp, University of North Carolina at Chapel Hill

Document Type

Article

Date of this Version

12-17-2014

Citation

Leamy et al.: Host genetics and diet, but not immunoglobulin A expression, converge to shape compositional features of the gut microbiome in an advanced intercross population of mice. Genome Biology 2014 15:552.

Comments

© 2014 Leamy et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License. Used by permission.

Abstract

Background: Individuality in the species composition of the vertebrate gut microbiota is driven by a combination of host and environmental factors that have largely been studied independently. We studied the convergence of these factors in a G₁₀ mouse population generated from a cross between two strains to search for quantitative trait loci (QTLs) that affect gut microbiota composition or ileal Immunoglobulin A (IgA) expression in mice fed normal or high-fat diets.

Results: We found 42 microbiota-specific QTLs in 27 different genomic regions that affect the relative abundances of 39 taxa, including four QTL that were shared between this G₁₀ population and the population previously studied at G4. Several of the G₁₀ QTLs show apparent pleiotropy. Eight of these QTLs, including four at the same site on chromosome 9, show significant interaction with diet, implying that diet can modify the effects of some host loci on gut microbiome composition. Utilization patterns of IghV variable regions among IgA-specific mRNAs from ileal tissue are affected by 54 significant QTLs, most of which map to a segment of chromosome 12 spanning the Igh locus. Despite the effect of genetic variation on IghV utilization, we are unable to detect overlapping microbiota and IgA QTLs and there is no significant correlation between IgA variable pattern utilization and the abundance of any of the taxa from the fecal microbiota.

Conclusions: We conclude that host genetics and diet can converge to shape the gut microbiota, but host genetic effects are not manifested through differences in IgA production.