Grant: Undergraduate Student Research Awards (USRA)

Depression and anxiety are prevalent mental health conditions that disproportionately affect females, who are more than twice as likely as males to be diagnosed with depression. This study aims to investigate the role of gut microbiota in mediating vulnerability to depressive and anxiety-like behaviours, with a specific focus on differentiating the contributions of sex chromosomes and gonadal hormones. Using the four-core genotype model, gut microbiota from mice with XX chromosomes and ovaries, XX chromosomes and testes, XY chromosomes and ovaries, and XY chromosomes and testes will be transplanted into wildtype (WT) male and female mice. WT recipients will then undergo the unpredictable chronic mild stress (UCMS) protocol to induce depressive-like behaviours. Postmortem analyses will explore neuroinflammatory markers, including chemocytokines and microglial activation, to determine whether gut microbiota effects on depressive-like phenotypes are mediated through immune system pathways. By comparing behavioural outcomes and immune markers, this work will elucidate whether susceptibility to UCMS is modulated by sex chromosomes, gonadal hormones, or their interaction. The findings will enhance our understanding of the interplay between gut microbiota, biological sex, and neuroimmune mechanisms in shaping mental health vulnerabilities.