BACKGROUND AND AIMS: The relationship between irritable bowel syndrome (IBS) and structural changes in various regional cortical areas remains unclear. Mendelian randomization (MR) was used to explore the potential association between IBS and Structural Brain Changes. METHODS: Genetically independent loci associated with IBS in individuals of European ancestry were selected as instrumental variants (IVs) in the large-scale genome-wide association studies (GWAS). Outcome data were obtained from 34 subregions of the cerebral cortex in a population of 51,665 individuals. MR analysis was performed to explore the potential association between IBS and cerebral cortex structure (surface area (SA) and thickness (TH)). Cochran's Q test, MR-Egger intercept test was used to examined heterogeneity and horizontal pleiotropy of single nucleotide polymorphisms (SNPs). "Leave-one-out" sensitivity analysis was conducted to assess the influence of individual SNPs. RESULTS: Five relationships were obtained from a total of 68 phenotypes in 34 subregional structures of the cerebral cortex. IVW analysis showed that IBS was associated with increased SA in the inferior temporal and rostral anterior cingulate regions (βSA=22.810 mm2, PSA=0.040
βSA=11.133 mm2, PSA=0.006). Additionally, IBS was associated with increased TH in the isthmus cingulate and pars opercularis regions (βTH=0.013 mm, PTH=0.043
βTH=0.010 mm, PTH=0.010), and decreased TH in the rostral anterior cingulate region (βTH=-0.009 mm², PTH=0.017). CONCLUSIONS: There is a potential association between IBS and the cerebral cortex structure. These findings provide important support for the association between diseases related to neurological damage and psychiatric abnormalities in IBS patients.