Peripheral Surgical Interventions and Psychiatric Outcomes: A Systematic Review of Gut-Brain-Immune Axis Mechanisms

Background The gut-brain-immune axis has emerged as a potential mediator in the development of psychiatric disorders. This systematic review examines associations between peripheral surgical interventions and psychiatric outcomes, with emphasis on potential underlying mechanisms involving microbiota, immune function, and neural signaling. Methods We conducted a systematic review following PRISMA guidelines, searching PubMed, EMBASE, and Cochrane databases from inception to May 2024. Studies examining associations between peripheral surgical procedures (appendectomy, vagotomy, tonsillectomy) and psychiatric outcomes were included. Risk of bias was assessed using appropriate tools for each study design. Results Eleven studies met inclusion criteria, including two large population-based cohort studies, one randomized controlled trial, and several mechanistic studies. Childhood appendectomy was associated with increased risk of mood disorders (adjusted hazard ratio [aHR] 1.19, 95% CI: 1.15–1.23) and anxiety disorders (aHR 1.20, 95% CI: 1.16–1.24), but not schizophrenia or obsessive-compulsive disorder. Truncal vagotomy was associated with mental health disorders (hazard ratio 1.22, 95% CI: 1.08–1.38), while selective vagotomy was not. Mechanistic studies identified alterations in inflammatory markers (TNF-α, IL-6), gut barrier function, and vagal signaling as potential mediators. Conclusions Limited evidence suggests that peripheral surgical interventions may be associated with increased risk of certain psychiatric disorders, possibly through gut-brain-immune axis mechanisms. However, the observational nature of most studies precludes causal inferences. The evidence base remains insufficient for clinical recommendations, particularly regarding obsessive-compulsive disorder and schizophrenia. Future research should focus on prospective studies with standardized biomarker assessments and longer follow-up periods.