Figure 2) Diurnal rhythms of the gut microbiota, host immunity and pathogen abundance across a) the active phase and b) the rest phase, as characterised in laboratory mice. SFB = Segmented Filamentous Bacteria.
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 pH29. 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 7,9,14,41,44,60. 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 phase7,11. 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 44. Notably, these pathways are mediated by the host innate immune system, with LPS and flagellin being detected by Toll-like receptors (TLRs)44. 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 influence cognitive processes and stress responses9. However, the link between microbial oscillations and circadian behaviour remains speculative.