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Gut microbiota as a transducer of dietary cues to regulate host circadian rhythms and metabolism

Nature Reviews Gastroenterology & Hepatology volume 18, pages 679–689 (2021)Cite this article

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Abstract

Certain members of the gut microbiota exhibit diurnal variations in relative abundance and function to serve as non-canonical drivers of host circadian rhythms and metabolism. Also known as microbial oscillators, these microorganisms entrain upon non-photic cues, primarily dietary, to modulate host metabolism by providing input to both circadian clock-dependent and clock-independent host networks. Microbial oscillators are generally promoted by plant-based, low-fat (lean) diets, and most are abolished by low-fibre, high-sugar, high-fat (Western) diets. The changes in microbial oscillators under different diets then affect host metabolism by altering central and peripheral host circadian clock functions and/or by directly affecting other metabolic targets. Here, we review the unique role of the gut microbiota as a non-photic regulator of host circadian rhythms and metabolism. We describe genetic, environmental, dietary and other host factors such as sex and gut immunity that determine the composition and behaviour of microbial oscillators. The mechanisms by which these oscillators regulate host circadian gene expression and metabolic state are further discussed. Because of the gut microbiota’s unique role as a non-photic driver of host metabolism and circadian rhythms, the development and clinical application of novel gut microbiota-related diagnostics and therapeutics hold great promise for achieving and maintaining metabolic health.

Key points

  • The gut microbiome has an essential role in transducing dietary cues used by central and peripheral host circadian clocks to regulate and adapt to shifts in energy balance.

  • Low-fat (lean) diets promote diurnal ‘oscillations’ of certain microbial populations that are metabolically relevant circadian drivers.

  • Western diets high in fat and refined sugars, and low in fibre influence key microbial oscillators to disrupt host circadian rhythms and metabolism to promote obesity.

  • The effects of microbial oscillators on host circadian networks and metabolism might involve the production of bioactive small molecules and metabolites.

  • Activation of nuclear receptors by microbiome-derived mediators is one of many mechanisms to regulate host transcriptional and epigenetic pathways that influence host circadian control of energy balance.

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Fig. 1: Crosstalk between host circadian clock and the gut microbiota.
Fig. 2: Lipid metabolism regulated through the control of host circadian network by the gut microbial components.

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Acknowledgements

The authors’ research is supported by grants from NIDDK (R01DK115221) and the Center for Interdisciplinary Study of Inflammatory Intestinal Diseases (P30 DK42086).

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Authors and Affiliations

  1. Department of Biological Engineering, Georgia Institute of Technology, Atlanta, GA, USA

    Hyoann Choi

  2. The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA

    Hyoann Choi

  3. Department of Physiology & Biophysics, University of Illinois at Chicago, Chicago, IL, USA

    Mrinalini C. Rao

  4. Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL, USA

    Eugene B. Chang

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All authors wrote and reviewed/edited the manuscript before submission. H.C. researched data for the article.

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Nature Reviews Gastroenterology & Hepatology thanks D. Haller, A. Zarrinpar and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Choi, H., Rao, M.C. & Chang, E.B. Gut microbiota as a transducer of dietary cues to regulate host circadian rhythms and metabolism. Nat Rev Gastroenterol Hepatol 18, 679–689 (2021). https://doi.org/10.1038/s41575-021-00452-2

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