Gut microbiome, immune function, and neuropsychiatric outcomes – examining causal relationships

Neuropsychiatric conditions represent a leading global health burden, with rising prevalence in younger populations and substantial treatment gaps despite existing pharmacological and psychological interventions. Emerging evidence implicates low-grade systemic inflammation, particularly elevated cytokines such as interleukin-6, as a potential causal contributor to a range of neuropsychiatric disorders including major depressive disorder and schizophrenia. The gut microbiome has gained attention as a modifiable factor influencing both neuropsychiatric risk and systemic immune activation. Altered microbial composition is consistently observed in individuals with neuropsychiatric conditions and is associated with gastrointestinal and immune dysregulation, suggesting a mechanistic pathway linking gut microbiota to brain health. However, causal relationships and underlying mechanisms remain poorly defined, as the literature is dominated by cross-sectional and observational studies. This PhD project aims to address these gaps using rigorous causal inference approaches to investigate the interplay between gut microbiota, immune function, and neuropsychiatric outcomes. Specific objectives include summarising existing evidence on gut-brain interactions, testing whether immune activation mediates the relationship between the gut microbiome and neuropsychiatric disorders, and evaluating the predictive potential of gut microbial profiles for neuropsychiatric conditions. Findings are expected to advance mechanistic understanding and inform novel preventative and therapeutic strategies.