Intestinal microbial circadian rhythms drive sex differences in host immunity and metabolism
Sarah K. Munyoki,
Julie P. Goff,
Antonija Kolobaric,
Armari Long,
Steven J. Mullett,
Jennifer K. Burns,
Aaron K. Jenkins,
Lauren DePoy,
Stacy G. Wendell,
Colleen A. McClung,
Kathleen E. Morrison,
Eldin Jašarević
Affiliations
Sarah K. Munyoki
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA
Julie P. Goff
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA
Antonija Kolobaric
Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA
Armari Long
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA
Steven J. Mullett
Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Health Sciences Mass Spectrometry Core, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Jennifer K. Burns
Clinical Translational Science Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Aaron K. Jenkins
Clinical Translational Science Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Lauren DePoy
Clinical Translational Science Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Stacy G. Wendell
Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Health Sciences Mass Spectrometry Core, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Colleen A. McClung
Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA; Clinical Translational Science Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Kathleen E. Morrison
Department of Psychology, West Virginia University, Morgantown, WV, USA
Eldin Jašarević
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA; Corresponding author
Summary: Circadian rhythms dynamically regulate sex differences in metabolism and immunity, and circadian disruption increases the risk of metabolic disorders. We investigated the role of sex-specific intestinal microbial circadian rhythms in host metabolism using germ-free and conventionalized mice and manipulation of dietary-derived fat, fiber, and microbiota-accessible carbohydrates. Our findings demonstrate that sex differences in circadian rhythms of genes involved in immunity and metabolism depend on oscillations in microbiota, microbial metabolic functions, and microbial metabolites. Further, we show that consuming an obesogenic, high-fat, low-fiber diet produced sex-specific changes in circadian rhythms in microbiota, metabolites, and host gene expression, which were linked to sex differences in the severity of metabolic dysfunction. Our results reveal that microbial circadian rhythms contribute to sex differences in immunity and metabolism and that dietary factors can entrain new circadian rhythms and modify the magnitude of sex differences in host-microbe circadian dynamics.
