Mechanisms of gut-brain axis involvement in ectotherm thermotolerance: "how the gut brain axis helps animals weather the heat

Climate change is critically impacting ecosystems and human societies globally and in the UK, threatening biodiversity, food security and economic stability. Temperature rises, and the lengthening of extreme heat episodes, pose a new and often understated threat not only to human life, but to animal life on land and in the sea. Climatic shifts lead to mismatched lifecycles between predators and preys, arrival of new plant, fungal, and animal invasive species, including new predators and parasites, but also exposure to temperatures endemic species are not adapted to. This critically threatens biodiversity, sadly exemplified by the decline in pollinator diversity. However, nature shows us that animal populations, even ectotherms that cannot regulate their body temperature, typically tolerate a range of temperatures, and that within a single species, different populations may develop adaptations to extreme temperatures, usually over tens to hundreds of generations. Characterising the natural genetic variability that has allowed wild animals to adapt to warmer temperatures can thus teach us about the physiological mechanisms of heat resilience.

However, animals are metaorganisms, meaning that they co-exist with communities of symbiotic microbes, most of them in their gut, called the gut microbiota. This has profound influences on animal health and behaviour. For instance, the gut microbiota influences appetite, taste, mood, mate selection, sleep, and its dysregulation can trigger autoimmune or neurodegenerative diseases, infections, metabolic syndrome, mood disorders or promote cancers. Therefore, it is not only animal genetics that need studying, but their interaction with the communities of microbes that live within. In particular, the connection between gut microbes and the brain is a major modulator of animal health, called the gut-brain axis (GBA), which has garnered much attention over the past decade. We know it is involved in many health processes throughout animal lifespan, including thermoregulation and resistance to heat, but this knowledge is fragmented. Hence, we critically lack the big picture that would allow us to 'hack' the GBA to improve animal resilience to heat.

How would we do that? We need to know about animal genetics and their gut microbiota composition, and study how they work together under environmental challenges (high temperature here) to impact animal physiology. Then we may develop pre- and pro-biotics that work well with an animal's genetic make-up and improve their health, or even boost their resistance to heat. This could be key for future-proofing our fisheries, poultry farms, and to protect pollinators critical for fruit and vegetable supplies.

Here, we gathered a team of experts from different universities and fields of research (microbiologists, evolutionary biologists, geneticists, cell biologists, biochemists, statisticians, bioinformaticians) to study the genetic and gut microbiota make-ups of wild bees, fish and worms living at different temperatures (warm and cool). This will allow us to identify microbes and animal genes (particularly in the brain) that are involved in animal adaptation to heat. We will then test whether the associations of animal genes and gut microbiota compositions we identified can improve thermotolerance in lab animals and study their effects on their metabolism, physiology, and brain activity. By studying three distant animal species, we will learn what mechanisms of thermotolerance are conserved and might be 'hacked' (with pre-/pro-biotics or drugs) to promote heat resilience in other species, possibly even in humans.