Host-microbe circadian dynamics: Finding a rhythm and hitting a groove in scientific inquiry

Abstract

Gut microbes are mediators of organismal-level circadian rhythms, responding to and transducing environmental cues. Gut microbes also exhibit rhythms, yet their contribution to a healthy microbiome remains unclear. We present our path to identifying host-microbe circadian dynamics related to health and outline a series of forward-thinking questions requiring further exploration.

Figure 1.. Environmental factors (i.e., diet) coupled with circadian disturbances (i.e., sleep loss or jet lag) significantly impact diurnal rhythms of gut microbes driving metabolic disruption

Circadian alignment (left panel) coupled with a balanced, low-fat, high-fiber diet and proper sleep results in normal oscillations of host-derived antimicrobial peptides (AMPs) in the gut with corresponding rhythms in relative abundance of ~20% of the bacterial community and microbial outputs, including secondary bile acids and short-chain fatty acids (SCFAs). Circadian disruptions (right panel) induced by diets high in saturated fat and sugar or disrupted sleep (i.e., jet lag) result in a loss of gut AMP rhythmicity, gut microbiota imbalances with overall decreased oscillations in relative abundance of specific microbial community members. However, under these conditions, “gain-of-function” microbial oscillations of certain community members and their outputs, such as H₂S and trimethylamine (TMA), are also observed and correspond with metabolic disruption. Several knowledge gaps remain that require further investigation to gain novel insights into host-microbe circadian interactions and define what constitutes a healthy microbiome.