Abstract
The mammalian gut harbors complex and variable microbial communities, across both host phylogenetic space and conspecific individuals. A synergy of host genetic and environmental factors shape these communities and account for their variability, but their individual contributions and the selective pressures involved are still not well understood. We employed barcoded pyrosequencing of V1-2 and V4 regions of bacterial small subunit ribosomal RNA genes to characterize the effects of host genetics and environment on cecum assemblages in 10 genetically distinct, inbred mouse strains. Eight of these strains are the foundation of the Collaborative Cross (CC), a panel of mice derived from a genetically diverse set of inbred founder strains, designed specifically for complex trait analysis. Diversity of gut microbiota was characterized by complementing phylogenetic and distance-based, sequence-clustering approaches. Significant correlations were found between the mouse strains and their gut microbiota, reflected by distinct bacterial communities. Cohabitation and litter had a reduced, although detectable effect, and the microbiota response to these factors varied by strain. We identified bacterial phylotypes that appear to be discriminative and strain-specific to each mouse line used. Cohabitation of different strains of mice revealed an interaction of host genetic and environmental factors in shaping gut bacterial consortia, in which bacterial communities became more similar but retained strain specificity. This study provides a baseline analysis of intestinal bacterial communities in the eight CC progenitor strains and will be linked to integrated host genotype, phenotype and microbiota research on the resulting CC panel.
Original language | English |
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Pages (from-to) | 2033-2044 |
Number of pages | 12 |
Journal | ISME Journal |
Volume | 6 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2012 |
Funding
We thank J Mosher, M Shakya, C Brandt, C Schadt (ORNL), M Hauser and J Becker (UTK) for many helpful discussions during data collection and analysis. We also thank L Miller (ORNL) for molecular biology assistance. We are also grateful to P Schloss (mothur; University of Michigan) and R Knight (UniFrac; University of Colorado) for guidance with their respective analytical tools. We also thank F Bushman (University of Pennsylvania) for critical evaluation of the manuscript and anonymous reviewers for helpful suggestions. This research was funded by the US Department of Energy Office of Science, Biological and Environmental Research programs at Oak Ridge National Laboratory (ORNL), by the Laboratory Directed Research and Development Program of ORNL and in part by a grant to MP from the National Human Genome Research Institute (NIH R01-HG004857). ORNL is managed by UT-Battelle, LLC, for the US Department of Energy under contract DE-AC05-00OR22725.
Keywords
- Collaborative Cross
- SSU rRNA gene
- intestinal microbial diversity
- microbiome
- microbiota
- pyrosequencing