Introduction
Circadian rhythms describe the synchronization of multiple biochemical and physiological processes across a 24-hour cycle, allowing organisms to anticipate predictable biotic and abiotic conditions across the day1. Circadian rhythms are self-sustaining in the absence of environmental cues, yet they are synchronised (‘entrained’) across multiple facets of physiology and behaviour by environmental cues. Light cues entrain the master pacemaker located in the brain, yet peripheral clocks in organs and tissues are largely entrained by non-photic cues such as temperature and feeding schedules2–5. Collectively, these cues interact with clock genes to influence 24-hour rhythms in gene expression6. Whilst food intake was previously thought to have localised effects on metabolic rhythms 7,8, mounting evidence points towards feeding being fundamental for orchestrating system-wide physiological homeostasis in innate immune function and metabolism across the day 3,9–14, even feeding back to influence the master clock 15. The far-reaching effects of food intake on host circadian rhythms are mediated by the gut microbiota, which rhythmically interact with the host to regulate rhythms in both innate immunity and metabolism10,11,13. However, despite a long-standing appreciation for the importance of both circadian rhythms1,4,16–19 and the gut microbiota20–25 for mediating host biological, ecological, and evolutionary processes, their interaction has largely been neglected in the study of natural populations.
Gut microbial communities are highly responsive to dietary and physiological cues, leading to high temporal variation within and across host individuals over months and years 26–28. However, the predictable dynamics of gut microbes over the day in response to food intake and host physiology has recently become a research focus for experimental studies on model systems. These have uncovered strong diurnal oscillations of the gut microbiota13,14,29–33 and metabolome 7,11, with bacterial numbers estimated to change 10-fold over the course of each day in laboratory mice 11. Indeed, gut microbial oscillations have been identified in captive settings from a diverse suite of species, from birds and mammals to fish13,26,31,32,34, and their effects often dominate over that of individual identity 32 3526,29. Microbial rhythms are underpinned by a combination of diet and time of feeding 36–39, yet are also under host circadian control: mice without functioning clock genes have disrupted gut microbial rhythms 40. Rhythms in gut microbial communities are therefore likely to be responses diurnal shifts in food intake and host physiology, rather than self-sustaining circadian rhythms.
Gut microbial rhythms are profoundly important for regulating host metabolism and innate immunity across the day7,8,41–44. Their disruption, for example due to jet lag in humans, leads to increased risk of metabolic disease, gut inflammation, and pathogen susceptibility 12,13,34. The importance of gut microbial rhythms for mediating both metabolic and immune homeostasis has broad implications for our understanding of gut microbiome function and their adaptive significance in natural populations. Circadian interactions between the gut microbiota and host immunity are of particular relevance for ecologists because pathogens are disproportionally important for mediating host fitness and evolutionary trajectories in natural populations45–47, with pathogen defence potentially being the principal evolutionary advantage of the gut microbiome48.
Diurnal oscillations in the gut microbiota are known to be strong, widespread across studied species, and have profound biological functions for the host. As such, research on host-microbe interactions in wildlife must begin to account for these daily dynamics. With an aim of encouraging the incorporation of circadian rhythms into wildlife microbiome research, we review hallmarks of gut microbial rhythms that have been identified across species, describe their molecular mechanisms, and outline how including microbial rhythms can advance our understanding of microbiota-mediated host-pathogen interactions and metabolic regulation in natural populations. Finally, we apply this information to provide recommendations for how to advance our understanding of gut microbial rhythms and their associations with host physiology in wildlife.