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

doi:10.1016/j.isci.2023.107999

Intestinal microbial circadian rhythms drive sex differences in host immunity and metabolism

iScience. 2023 Sep 22;26(10):107999. doi: 10.1016/j.isci.2023.107999. eCollection 2023 Oct 20.

Authors

Sarah K Munyoki^{1

2

3}, Julie P Goff^{1

2

3}, Antonija Kolobaric⁴, Armari Long^{1

2

3}, Steven J Mullett^{5

6}, Jennifer K Burns^{7

8}, Aaron K Jenkins^{7

8}, Lauren DePoy^{7

8}, Stacy G Wendell^{5

6}, Colleen A McClung^{4

7

8}, Kathleen E Morrison⁹, Eldin Jašarević^{1

2

3}

Affiliations

¹ Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
² Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
³ Magee-Womens Research Institute, Pittsburgh, PA, USA.
⁴ Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
⁵ Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
⁶ Health Sciences Mass Spectrometry Core, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
⁷ Clinical Translational Science Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
⁸ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
⁹ Department of Psychology, West Virginia University, Morgantown, WV, USA.

Abstract

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.

Keywords: Human metabolism; Microbiology; Microbiome.

Abstract

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