Impact of nutrition and helminth infection on gut health and the microbiome using a lab-to-wild mouse mode

Abstract

The mammalian gastrointestinal tract is a rich ecosystem composed of complex interactions. It is home to a diverse community of bacterial microbes known as the gut microbiota, the preferential niche for many helminth parasites and the largest site of both the immune system and diet-derived nutrient absorption. To date, most studies exploring the relationship between nutrition, helminth infection and immunity, and the gut microbiota have utilised controlled laboratory-rodent models, with intentionally limited genetic, ecological, and behavioural variation. While these controlled studies have been very valuable for understanding mechanisms, they are limited in their ability to extrapolate the outcome of these interactions to natural populations. Using a lab-to-wild mouse model, with both wild and laboratory-reared wood mice (Apodemus sylvaticus), the key aim of my thesis is to use this unique approach to both elucidate the impacts of nutrition and helminth infection on the gut microbiota and health in the lab, and then importantly to test the consequences of these interactions in the wild.

First, I characterised the gut microbiota of our recently derived paired laboratory wood mouse colonies, and found that our formerly wild, but laboratory-reared wood mice had a wild-like gut microbiota (Wild-like: A. sylvaticus), similar, although less diverse than wild wood mice. In contrast, our recently caesarean re-derived wood mouse colony, who were fostered by standard laboratory mice (Mus musculus) had a more lab-like gut microbiota (Lab-like: A. sylvaticus), but also shared many bacterial taxa with other Wild-like:As mice. Then, I investigated how these Wild-like:As and Lab-like:As colonies responded to infection with the gastrointestinal helminth, Heligmosomoides polygyrus, which is a natural parasite of wood mice within the wild. I assessed how the diversity and stability of the microbiota composition was altered over the course of infection and determined if this differed between the two colonies. I found that immune responses differed between the two wood mouse colonies and that this was impacted by helminth infection, whereby infection was associated with a decrease in gut-microbiota diversity of Wild-like:As mice, but not Lab-like:As mice.

Previously, we have shown that wood mice given a high-quality supplemented diet, were more resistant to helminth infection and generated stronger immune responses, in both the wild and our wild-like colony. Here, I expanded upon the findings of this earlier study, by investigating the role of the gut microbiota on the impact of high-quality diet supplementation and improving helminth resistance. I found that nutrition and to a lesser extent helminth infection significantly drive the microbiota composition and diversity in both lab and wild wood mice; and could be, in part, important in driving the impact of nutrition on helminth immunity.

Overall, this thesis both develops an exciting new lab-to-wild mouse model that will enable both mechanistic studies in the lab, and fitness-relevant experiments in the field to better understand the complex interactions between nutrition, infection, the gut microbiota, and health. Importantly, my results show that the gut microbiota is an important player in the gut ecosystem, and my results provide a greater understanding of how the interplay between nutrition, immunity and helminthiasis can impact host health and infection dynamics.