Cerebral cortex changes in FD, IBS, and GERD: A Mendelian randomization study

Background: Prospective and cross-sectional studies have reported an association between functional gastrointestinal disorders and anxiety and depression. However, the causal relationship remains uncertain. To clarify this, we utilized Mendelian randomization (MR) to assess the causal effects of common gastrointestinal disorders on cortical structures.

Methods: Genome-wide association study (GWAS) data was gathered for functional dyspepsia (FD), irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD) from European populations numbering 329,262, 16,792, and 602,604, respectively. GWAS cerebral cortical architecture data for cortical thickness (TH) and surface area (SA) were obtained from 51,665 MRI scans. MR was used to analyze the casual relationship between FD, IBS, GERD, and cortical structures. Inverse-variance weighted, weighted median, and MR-Egger tests were performed as assessment indicators. We also evaluated heterogeneity and pleiotropy.

Results: FD significantly decreases the TH in the rostral anterior cingulate cortex (β_TH = -0.022 mm; 95%CI: -0.035 mm to -0.009 mm²; P_TH = 6.89 × 10^-4), and IBS significantly decreases the SA of the pars triangularis (β_SA = -21.91 mm²; 95%CI: -32.99 mm to -10.83 mm²; P_SA = 1.06 × 10^-4), precuneus (β_SA = -47.53 mm²; 95%CI: -73.57 mm to-21.48 mm²; P_SA = 3.48 × 10^-4) and superior frontal regions (β_SA = -78.70 mm²; 95%CI: -122.61 mm to -34.78 mm²; P_SA = 4.4 × 10^-4). At the local functional level, GERD significantly increases the SA of the inferior temporal region (β_SA = -113.58 mm², 95%CI: -113.58 mm to -39.01 mm², P_SA = 6.05 × 10^-5).

Conclusions: FD, IBS and GERD can affect the cerebral cortex architecture through the brain-gut axis, potentially increasing the risks of mental illness and cognitive impairment.