The Role of the Gut Microbiome in the Social Stress Response

The gut microbiome has considerable influence over host health, and so alterations to its composition can result in disease. Research has demonstrated that environmental stress, including social contact, can influence lifespan. This is potentially dependent on changes in the microbiome, facilitated through gut-brain communication via the gut-brain axis. This thesis utilised a Drosophila melanogaster model to explore the interplay between the microbiome and responses to social stress. Previous research demonstrating the sensitivity of the male Drosophila microbiome to the social environment positioned it as a likely candidate for a modulator of various social responses. This thesis provides evidence for a causal pathway, implicating the microbiome in shaping the male longevity response to same-sex social contact, with antibiotic impact varying with the social environment. An involvement of the microbiome in the cognitive response, but not the mating response, was also established, alongside the expression of genes associated with cognitive development. There was some evidence for the role of the microbiome in behaviour, and for a slight protective effect of the age of the rival on socially-driven age-associated changes in behaviour. Additionally, KEGG predicted functional analysis was employed to infer microbial effects on host gene function in studies that observed a microbiome change, identifying pathways that may influence ageing. Subsequently, gene expression analysis determined one of these host pathways to be dependent on the microbiome. In conclusion, this thesis provides evidence that same-sex social contact in male Drosophila alters the microbiome in a way that reduces lifespan and triggers the cognitive response, which can be partially replicated in single flies by antibiotic perturbation. Furthermore, many responses were altered in an age-dependent way, interacting with senescence and possibly age-associated dysbiosis. These findings hold implications for leveraging the microbiome to develop targeted interventions against disease, particularly in the context of ageing.