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

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. This Review explores how the gut microbiota acts as a driver and regulator of host circadian rhythms and metabolism, highlighting its unique role in transducing dietary cues. Key determinants of microbial oscillations and insights into microbial control of chronometabolism are discussed. 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 tran