Previous Article A Microbe Associated with Sleep Revealed by a Novel Systems-Genetic Analysis of the Microbiome in Collaborative Cross Mice Jason A. Bubier , Vivek M. Philip , Christopher Quince , James Campbell , Yanjiao Zhou , Tatiana Vishnivetskaya , Suman Duvvuru , Rachel Hageman Blair , Juliet Ndukum , Kevin D. Donohue , Carmen M. Foster , David J. Mellert , George Weinstock , Cymbeline T. Culiat , Bruce O'Hara , Anthony V. Palumbo , Mircea Podar and Elissa J. Chesler Genetics Early online January 2, 2020; https://doi.org/10.1534/genetics.119.303013 Jason A. Bubier Info & Metrics Abstract 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 ( Bactoroidales Porphyromonadeceae ) abundance and sleep phenotypes. In a test of this association in the BKS.Cg-Dock7 m +/+ Lepr db /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.