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Cell Host Microbe. 2015 May 13;17(5):681-9. doi: 10.1016/j.chom.2015.03.006. Epub 2015 Apr 16.

Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism.

Author information

1
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
2
Institute for Genomics and Systems Biology, Argonne, IL 60439, USA; Graduate Program in Biophysical Sciences, The University of Chicago, Chicago, IL 60637, USA.
3
Graduate Program in Biophysical Sciences, The University of Chicago, Chicago, IL 60637, USA; Medical Scientist Training Program, The University of Chicago, Chicago, IL 60637, USA.
4
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
5
Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.
6
Graduate Program in Biophysical Sciences, The University of Chicago, Chicago, IL 60637, USA; James Frank Institute, The University of Chicago, Chicago, IL 60637, USA; Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA.
7
Institute for Mind and Biology, The University of Chicago, Chicago, IL 60637, USA.
8
Institute for Genomics and Systems Biology, Argonne, IL 60439, USA; Department of Ecology and Evolution, The University of Chicago, Chicago, IL 60637, USA.
9
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA. Electronic address: echang@medicine.bsd.uchicago.edu.

Abstract

Circadian clocks and metabolism are inextricably intertwined, where central and hepatic circadian clocks coordinate metabolic events in response to light-dark and sleep-wake cycles. We reveal an additional key element involved in maintaining host circadian rhythms, the gut microbiome. Despite persistence of light-dark signals, germ-free mice fed low or high-fat diets exhibit markedly impaired central and hepatic circadian clock gene expression and do not gain weight compared to conventionally raised counterparts. Examination of gut microbiota in conventionally raised mice showed differential diurnal variation in microbial structure and function dependent upon dietary composition. Additionally, specific microbial metabolites induced under low- or high-fat feeding, particularly short-chain fatty acids, but not hydrogen sulfide, directly modulate circadian clock gene expression within hepatocytes. These results underscore the ability of microbially derived metabolites to regulate or modify central and hepatic circadian rhythm and host metabolic function, the latter following intake of a Westernized diet.

PMID:
25891358
PMCID:
PMC4433408
DOI:
10.1016/j.chom.2015.03.006
[Indexed for MEDLINE]
Free PMC Article

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