Intersection of the Gut Microbiome and Circadian Rhythms in Metabolism

Abstract

The gut microbiome and circadian rhythms (CRs) both exhibit unique influence on mammalian hosts and have been implicated in the context of many diseases, particularly metabolic disorders. It has become increasingly apparent that these systems also interact closely to alter host physiology and metabolism. However, the mechanisms that underlie these observations remain largely unknown. Recent findings have implicated microbially derived mediators as potential signals between the gut microbiome and host circadian clocks; two specific mediators are discussed in this review: short-chain fatty acids (SCFAs) and bile acids (BAs). Key gaps in knowledge and major challenges that remain in the circadian and microbiome fields are also discussed, including animal versus human models and the need for precise timed sample collection.

Keywords: bile acids; circadian rhythms; metabolism; microbiome; short-chain fatty acids.

Figure 1:. Microbe-derived mediators that influence host metabolic outcomes.

Inputs to the host that can include altered diet, feeding schedule (such as time-restricted feeding), or circadian rhythm disruption (by genetic deletion of core clock genes or jet lag protocol in animal models), which can significantly affect the synthesis, metabolism, and dynamics of gut microbe-derived metabolites. SCFAs and modified secondary bile acids are two such groups of metabolites that also exhibit oscillations and influence host CRs, both of which are subject to changes of the preceding inputs. Gain or loss of gut mediators as oscillators can alter host metabolism, although specific dynamics concerning how this occurs has not been thoroughly described. As illustrated by the studies discussed in this review, both of these metabolite groups exhibit unique influence on host outcomes, particularly relating to metabolism and circadian rhythm expression.