Interactions between food intake, mucosal commensals, and sIgA together regulate gut microbial oscillations over the day. However, an additional mechanism that has received less attention is the role of ecological dynamics in regulating microbial oscillations. An increase in gut microbes post-feeding alter the chemistry of the gut, increasing CO2 and methane levels and decreasing the pH 29. Changes to gut conditions after rapid proliferation of microbes post-feeding may be less favourable for many microbes, potentially contributing to the consequent reduction in the bacterial population late in the active phase despite food still being available and probably ingested. Changes to gut conditions may therefore reinforce microbial rhythms by ensuring that they are only triggered once at first food intake after fasting. This pattern is supported by microbial dynamics in wild meerkats, where bacterial load peaks after dawn foraging, but not in the late afternoon prior to sunset when meerkats forage a second time 26.
Whilst we focus here on mechanisms underpinning interactions between gut bacteria and the innate immune system, gut microbial rhythms also trigger molecular cascades that regulate metabolism and hormone production across the day 7,9,14,45,48,64. Circadian changes to some bacterial metabolites, such as short-chain fatty acids (SCFAs) and bile acids, are particularly important for upregulating lipid metabolism and absorption during the active phase 7,11. The bacterial compounds lipopolysaccharide (LPS) and flagellin, which are found in the cell walls of gram-negative bacteria, have also been implicated in the diurnal dynamics of body weight and corticosterone synthesis in mice 48. Notably, these metabolic pathways are mediated by the host innate immune system, with LPS and flagellin being detected by Toll-like receptors (TLRs) 48,65. Upon contact with LPS, TLRs initiate the release of α-defensin 66, which increases mucosal defences against ingested bacteria during feeding 67. In addition, the gut microbiota also generate neuro-active metabolites such as tryptophan and serotonin, therefore oscillations of the gut microbiota may cause circadian rhythms in neuro-active compounds that can directly communicate with the nervous system and HPA axis, thereby potentially influencing cognitive processes, stress responses and behaviour 9. However, the link between microbial oscillations and circadian behaviour remains speculative.
Avenues of future research
A major objective for future investigations on the daily rhythms of the gut microbiome is to quantify their prevalence and strength across natural populations. Currently, our knowledge on gut microbial oscillations largely stems from laboratory mice, whilst our understanding of circadian rhythms of wildlife is largely restricted to behaviour 68. To understand the adaptive significance of circadian rhythms and their entrainment by the gut microbiota, we need to move the study of circadian rhythms to natural populations 69. This is because feeding times and diet of captive animals generally do not mirror foraging regimes of wild counterparts, and, together with microbial transmission between captive animals and humans, leads to captive animals having perturbed and ‘humanised’ gut microbiotas 70,71. Furthermore, many complex ecological processes are difficult or impossible to replicate in captivity. As such, whilst studies on captive animals can disentangle drivers of circadian rhythms, they may not actually reflect circadian rhythms in nature. A first step is to simply account for time of day samples were collected in analyses. Below we briefly outline how integrating gut microbiome and circadian rhythm in wildlife research can advance several outstanding questions in ecology (Fig. 4).