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.