Circadian rhythms and the gut microbiome synchronize the host’s metabolic response to diet

Gutierrez Lopez DE, Lashinger LM, Weinstock GM, Bray MS. Circadian rhythms and the gut microbiome synchronize the host’s metabolic response to diet. Cell Metab. 2021 May 4;33(5):873-887. doi: 10.1016/j.cmet.2021.03.015. Epub 2021 Mar 30. PMID: 33789092.


The molecular circadian clock and symbiotic host-microbe relationships both evolved as mechanisms that enhance metabolic responses to environmental challenges. The gut microbiome benefits the host by breaking down diet-derived nutrients indigestible by the host and generating microbiota-derived metabolites that support host metabolism. Similarly, cellular circadian clocks optimize organismal physiology to the environment by influencing the timing and coordination of metabolic processes. Host-microbe interactions are influenced by dietary quality and timing, as well as daily light/dark cycles that entrain circadian rhythms in the host. Together, the gut microbiome and the molecular circadian clock play a coordinated role in neural processing, metabolism, adipogenesis, inflammation, and disease initiation and progression. This review examines the bidirectional interactions between the circadian clock, gut microbiota, and host metabolic systems and their effects on obesity and energy homeostasis. Directions for future research and the development of therapies that leverage these systems to address metabolic disease are highlighted.


Our findings support the hypothesis that poor host metabolic outcomes are the result of asynchronous feeding signals, out of coordination with the light entrained circadian clock-driven anticipatory mechanisms regulating nutrient absorption and utilization, which may indirectly affect GM composition throughout the day. Small, achievable changes in behavior (e.g., changing timing of macronutrient consumption and improved sleep hygiene) that modulate GM signaling may harness innate biology to overcome the obesogenic environment that imposes a potential detriment to human health.

Publication History

Published online: March 30, 2021



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