Introduction
Circadian rhythms describe the synchronization of multiple biochemical and physiological processes across a 24-hour cycle, allowing organisms to anticipate and respond to predictable biotic and abiotic conditions across the day 1. 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 schedules 2–5. Collectively, these cues interact with clock genes to influence 24-hour rhythms in gene expression 6. 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 periodically interact with the host to regulate rhythms in both innate immunity and metabolism 10,11,13, and potentially the gut-brain axis 9. However, despite a long-standing appreciation for the importance of both circadian rhythms 1,4,16–19 and the gut microbiota 20–25 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. Recently, gut microbial dynamics over the course of a day has become a research focus for experimental studies on model systems. These have uncovered strong diurnal oscillations of the gut microbiota 13,14,29–33 and metabolome 7,11, with bacterial numbers estimated to change 10-fold over the course of each day in laboratory mice 11. Gut microbial oscillations have been identified in several species in captivity, from birds and mammals to fish 13,31,32,34, and these oscillations are often strong enough to mask identify effects 29,32,35. Similar findings were recently demonstrated in a wild population of meerkats 26, which tend to forage in the early morning and again in the evening (Fig. 1a). Peaks in foraging corresponded with shifts in many microbial taxa, with Clostridium in particular peaking strongly at dawn and declining in the afternoon (Fig. 1b). These shifts between sunrise and sunset structured the entire ecological community (Fig. 1c). Whereas time of feeding and diet largely govern these microbial rhythms36–39, genetically-coded immune regulation by the host is a crucial contributing factor: mice lacking clock genes have disrupted gut microbial rhythms 40. Together, these studies suggest that microbial oscillations may be widespread across host species and that they are likely in response diurnal shifts in food intake and clock-encoded rhythms in host physiology, rather than self-sustaining circadian rhythms.
Seasonal rhythms in the gut microbiota are known to modulate energy metabolism 41–43, and potentially pathogen susceptibility 41. Consequently, short-term gut microbial oscillations across the day are likely equally important to biological function 7,8,45–48. The disruption of gut microbial rhythms, for example due to jet lag in humans, leads to increased risk of metabolic disease, gut inflammation, and pathogen susceptibility 12,13,34. Circadian interactions between the gut microbiota and host immunity are of particular relevance for evolutionary ecologists because pathogens are disproportionally important for mediating host fitness and evolutionary trajectories in natural populations 49–51, with pathogen defence suggested to be the principal evolutionary advantage of the gut microbiome 52. Understanding the role of gut microbial rhythms in mediating host immune and metabolic homeostasis in natural populations would elucidate the functional importance and adaptive significance of gut microbiome rhythms for individual fitness and, more generally, wildlife health.
In summary, diurnal oscillations in the gut microbiota are known to be strong, widespread across model species, and have profound biological functions for the host. As such, it is important for research on host-microbe interactions in wildlife to account for these daily dynamics. With the aim to encourage 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 wildlife 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 and health in wildlife.