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

Genetics. 2020 Mar;214(3):719-733. doi: 10.1534/genetics.119.303013. Epub 2020 Jan 2.


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.

Keywords: behavior; bioinformatics; genetics; genomics; sleep.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacteroides / genetics
  • Chromosomes, Human, Pair 7 / genetics
  • GTPase-Activating Proteins / genetics*
  • Gastrointestinal Microbiome / genetics
  • Genomics
  • Genotype
  • Guanine Nucleotide Exchange Factors / genetics*
  • Humans
  • Mice
  • Obesity / genetics*
  • Obesity / microbiology
  • Obesity / physiopathology
  • Receptors, Leptin / genetics*
  • Sleep / genetics*


  • Anti-Bacterial Agents
  • Dock7 protein, mouse
  • GTPase-Activating Proteins
  • Guanine Nucleotide Exchange Factors
  • Receptors, Leptin
  • leptin receptor, mouse