A Microbe Associated with Sleep Revealed by a Novel Systems-Genetic Analysis of the Microbiome in Collaborative Cross Mice.

Jason A. Bubier, The Jackson Laboratory
Vivek M. Philip, The Jackson Laboratory
Christopher Quince
James Campbell
Yanjiao Zhou, The Jackson Laboratory
Tatiana Vishnivetskaya
Suman Duvvuru
Rachel Hageman Blair
Juliet Ndukum, The Jackson Laboratory
Kevin D Donohue
Carmen M Foster
David J Mellert
George M. Weinstock, The Jackson Laboratory
Cymbeline T Culiat
Bruce O'Hara
Anthony V Palumbo
Mircea Podar
Elissa J Chesler, The Jackson Laboratory

Jennifer Ryan, Neil Cole, Christine Rosales, Laura Anderson and Samantha 636 Burrill conducted db sleep studies and dissections.


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 quantitative trait loci and correlated the abundance of cecal mRNA, luminal microflora, physiology and behavior in a highly diverse Collaborative Cross breeding population. One such relationship, regulated by a variant on Chr 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 relations extracted from this study can be used to interrogate other diseases, microbes and mechanisms.