Potential Role for the Gut Microbiota in Modulating Host Circadian Rhythms and Metabolic Health

Abstract

This article reviews the current evidence associating gut microbiota with factors that impact host circadian-metabolic axis, such as light/dark cycles, sleep/wake cycles, diet, and eating patterns. We examine how gut bacteria possess their own daily rhythmicity in terms of composition, their localization to intestinal niches, and functions. We review evidence that gut bacteria modulate host rhythms via microbial metabolites such as butyrate, polyphenolic derivatives, vitamins, and amines. Lifestyle stressors such as altered sleep and eating patterns that may disturb the host circadian system also influence the gut microbiome. The consequent disruptions to microbiota-mediated functions such as decreased conjugation of bile acids or increased production of hydrogen sulfide and the resultant decreased production of butyrate, in turn affect substrate oxidation and energy regulation in the host. Thus, disturbances in microbiome rhythms may at least partially contribute to an increased risk of obesity and metabolic syndrome associated with insufficient sleep and circadian misalignment. Good sleep and a healthy diet appear to be essential for maintaining gut microbial balance. Manipulating daily rhythms of gut microbial abundance and activity may therefore hold promise for a chrononutrition-based approach to consolidate host circadian rhythms and metabolic homeorhesis.

Keywords: chronodisruption; clock genes; gut microbiome; plant food; prebiotics; sleep/wake rhythm.

Figure 1

Circadian rhythm, gut microbiota, and metabolism. The light/dark cycle is the Zeitgeber for the central clock in the brain, while signals from the brain entrain peripheral clocks, e.g., in the intestine. Intestinal bacteria also show diurnal fluctuations in terms of their abundance and functions. Host controlled behaviors such as sleep, diet (food composition, timing of eating a meal), light exposure, and stimulants (e.g., caffeine) may potentially affect intestinal rhythms of metabolism. New evidence indicates that gut microbiota influences circadian rhythms, with consequent impact on the metabolic homeostasis of the host (Figure adapted from [1]).

Figure 2

Potential mechanism of gut microbiota interactions in the circadian–metabolic axis. Host behavior, sleep, and diet control gut bacteria, which in turn show changes in terms of microbial composition and functional genome in a rhythmic manner. Circadian rhythms may be affected by microbial metabolites such as butyrate, secondary bile acids, and microbially synthesized vitamins, and potentially disrupted by hydrogen sulphide. The immediate effects on energy resources for colonic epithelial cells, and peripheral effects on substrate oxidation via systemic circulation potentially impact energy homeostasis.