2) Gut microbial rhythms and pathogen defence
In mice, gut microbial oscillations increase host resistance to gut
pathogens such as Salmonella during the active phase by
triggering the release of AMPs into the gut 13.
Reducing the abundance of mucosal commensal SFB increases host
susceptibility to Salmonella infection and also removes circadian
rhythms in susceptibility 13, demonstrating that the
rhythmic activity of gut mucosal commensals is a key mechanism governing
microbiome-mediated pathogen defence. Testing for associations between
the abundance and rhythmicity in mucosal commensals and infection status
may therefore be a more effective method of uncovering the link between
the gut microbiota and pathogen susceptibility than focusing on overall
gut microbial diversity. Arhythmic gut microbial communities have been
linked to disease in humans 34, and therefore it might
be expected that individuals with disrupted or dampened gut microbiota
rhythms are more susceptible to infection (Fig. 3).
Circadian rhythms in animal susceptibility and pathogen reproduction and
transmission are well documented 18,72, with hosts and
parasites having coevolved defensive and offensive rhythms,
respectively. Yet the role of the gut microbiota in mediating infection
outcomes is unclear and many questions remain. Do gut microbial rhythms
protect the host against a broad range of pathogens, or are they only
effective for specific gut pathogens? Microbial rhythms control the
release of AMPs, which are effective against a wide range of pathogens
including bacteria, fungi and viruses 73. Thus, it is
likely that microbial rhythms protect the host against a broad range of
pathogenic agents entering the gut. However, the gut is not the only
entry point of pathogens and it remains unknown whether microbial
rhythms also play a role in pathogen defence more generally.
Even less explored is the connection between gut microbial oscillations
and adaptive immunity, which is an essential pillar of resistance again
recurring parasitic challenges in jawed vertebrates74. Gut microbiome disruption impairs antibody
responses in mice 75, and gut microbial metabolites
influence the expression of the mammalian circadian clock genePer2 7,76, which is responsible for mounting
both innate and adaptive responses to infection 77.
Investigating which components of the gut microbiota affect the
expression of clock genes and in which ecological contexts may identify
the mechanisms by which the microbiota shape pathogen defence.