The microbiome influences health and disease through complex networks of host genetics, genomics, microbes, and environment. Identifying the mechanisms of these interactions has remained challenging. Systems genetics in laboratory mice (Mus musculus) enables data-driven discovery of biological network components and mechanisms of host-microbial interactions underlying disease phenotypes. To examine the interplay among the whole host genome, transcriptome, and microbiome, we mapped QTL and correlated the abundance of cecal messenger RNA, luminal microflora, physiology, and behavior in a highly diverse Collaborative Cross breeding population. One such relationship, regulated by a variant on chromosome 7, was the association of Odoribacter (Bacteroidales) abundance and sleep phenotypes. In a test of this association in the BKS.Cg-Dock7m +/+ Leprdb/J mouse model of obesity and diabetes, known to have abnormal sleep and colonization by Odoribacter, treatment with antibiotics altered sleep in a genotype-dependent fashion. The many other relationships extracted from this study can be used to interrogate other diseases, microbes, and mechanisms.
|Number of pages||15|
|State||Published - 2020|
Bibliographical noteFunding Information:
David Durtschi, Gene Barker, and Ann Wymore performed genotyping and gene expression analysis for all samples. Darla Miller worked with the Collaborative Cross at Oak Ridge National Laboratory (ORNL). Matthew Vincent produced the “deSNPed” version of the Illumina probes for the Collaborative Cross founder strains. Jennifer Ryan, Neil Cole, Christine Rosales, Laura Anderson, and Samantha Burrill conducted db sleep studies and dissections. This research was sponsored by the Laboratory Directed Research and Development Program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the U. S. Department of Energy, under contract DE-AC05-00OR22725. J.A.B. was funded by National Institute on Drug Abuse grant U01 DA-043809.
Copyright © 2020 Bubier et al.
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