Alice Risely: Why time of day matters when studying host-microbe interactions

In our new post, Dr. Alice Risely—who will start a Research Fellowship at Salford University, UK in March—discusses her recently published paper, “Circadian rhythms of hosts and their gut microbiomes: implications for animal physiology and ecology.” Alice elucidates on the link between gut microbiomes and circadian rhythms, ideas for future research, and reminisces on her childhood fascination with animals.

About the paper

So many processes in ecology revolve around timing. One’s timing must be right to avoid predators, find a mate, migrate, and release seeds. The temporal expression of physiological and behavioural traits is therefore of tremendous importance for understanding ecological interactions and community patterns. Most scientists analytically control for temporal variation by including variables such as month and year in statistical models; however, very short-term variations, like time of day, are often ignored. This goes against what we know from decades of research—that time of day is a hugely important predictor of behaviour and physiology. Time of day is so crucial that a 24h clock is encoded in the genes of almost all organisms which generate time-appropriate responses in physiology and behaviour. These are called circadian rhythms, and their genetic architecture and expression varies across individuals, generating individual variation in circadian phenotypes.

A figure from our perspective piece visualising the migration of segmented filamentous bacteria (the long and segmented microbes) to the mucosal layer in the active phase.

I study animal microbiomes, and my colleagues and I wrote a perspective piece on why circadian rhythms matter when studying host-microbe interactions. The perspective was inspired by results from earlier work we did on meerkats (Risely et al. Nat Comms 2021), which found that the faecal microbiota of this species shifted dramatically between the morning and afternoon. This was a shock, because I had only investigated time of day to control for any minor effects it may have, and I was surprised that it was such as dominant predictor. When I reported these results to peers, there was a lot of scepticism. Lots of people thought these effects were just shedding patterns and did not reflect conditions in the gut. I decided to investigate this topic further and the idea for this perspective paper was born.

About the research

One of the main messages of the perspective is simply to highlight that the gut microbiome can change considerably across the day, and there is mounting evidence from experimental systems that these rhythms are an important facet of microbiome function. The perspective outlines the hallmarks of gut microbial rhythms described to date, delves into the mechanisms, and highlights some interesting questions that arise from these new insights. Anyone studying microbiomes should therefore consider reporting time of day effects in their studies so that we can start building up knowledge on these processes. One contributing factor driving these oscillations may be foraging patterns, and therefore species that have specific foraging times (such as meerkats or other predators) may demonstrate stronger rhythms than those that graze all day (e.g., grazing herbivores).  

A wild meerkat studied as part of the Kalahari Meerkat Project in South Africa. Meerkat gut microbiomes undergo big shifts over the day (credit: Alice Risely)

In my opinion, one of the most promising advances happening in this field right now is the build-up of evidence that certain bacterial strains are disproportionately important for host function, including the regulation and breakdown of host circadian rhythms. These taxa populate the mucosal lining of the gut and have special architecture that allows them to physically anchor themselves to the host epithelium. In the perspective, we highlight one particularly important group called segmented filamentous bacteria (SFBs), which taxonomically belong to Clostridiales and are found across all mammals and potentially other clades too, including birds. They do all sorts of interesting things, including undergoing daily micro-migrations between the gut lumen and the mucosal layer where they anchor to the host epithelium and trigger the mass release of immune peptides when animals wake up and become active. I think an important next step for the field is to begin focusing on these mucosal taxa, because they represent our best bet for identifying true gut symbionts. This does not mean dissecting all study animals; however, some specimens are required to get samples from the mucosal layer of the small intestine which can then be used to identify which strains (or ASVs) are common in this microhabitat. These can then be monitored in the faecal microbiota using non-invasively collected samples.

About the author

Alice Risely hiking in the German Alps

I was a postdoc at Ulm University in south Germany and am about to start a research fellowship at Salford University in Manchester, so I am just about to become independent which is really exciting. As part of my fellowship I want to study how global change processes, such as urbanisation, are promoting the evolution of microbial pathogenicity within the context of a complex microbiome, and ask whether this process is increasing zoonotic disease risk. There is currently a lot of focus on viral pathogens, but some of the most common and serious zoonotic pathogens are gut bacteria (e.g., Salmonella), which can additionally spread antibiotic resistance. I want to look at these questions in gulls—which have massively changed their ecology in the last 20 years to exploit urban habitats—so if you study gulls (especially urban gulls) and want to collaborate then please contact me!

I became interested in ecology mostly because I was an animal lover. I never lost that childhood sense that animals are just like us—complex, emotional beings. When I was young, if I accidently killed a spider I would be devastated. That sense still shapes my identity as a scientist because I am passionate about scientific ethics, in terms of how we as scientists treat both study animals and other people (we are just animals after all). I think institutions like BES are great because they talk a lot about ethics and really promote inclusive behaviour and tackle inequality head on. Nevertheless, I witness and hear about bad practices and academic bullying all the time and I think it’s still a big problem in science. Bullying can take many insidious forms—spreading gossip, blocking publications, the threat of negative references, etc. I’d love to see a bit more focus on tackling that and making sure all ecologists are protected from such experiences.

Enjoyed the post? Read the research here!

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