Inflammatory bowel diseases, interleukin-6 and interleukin-6 receptor subunit alpha in causal association with cerebral cortical structure: a Mendelian randomization analysis

• Published in: Frontiers in immunology Vol. 14; p. 1154746
• Main Authors: Liu, Chunlong, Zhu, Shijie, Zhang, Jian, Ren, Kuiwu, Li, Kangkang, Yu, Jiangtao
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 20.04.2023
• Subjects: brain cortical structure; Cerebral Cortex - metabolism; Crohn’s disease; Genome-Wide Association Study; Humans; IL-6; IL-6Rα; Immunology; inflammatory bowel disease; Inflammatory Bowel Diseases - genetics; Interleukin-6 - genetics; Interleukin-6 - metabolism; Mendelian Randomization Analysis; Receptors, Interleukin-6 - genetics; ulcerative colitis; brain cortical structure; ulcerative colitis; Mendelian randomization; IL-6Rα; IL-6; inflammatory bowel disease; Crohn’s disease
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1154746

Neurological involvement and psychiatric manifestations have been documented in clinical cases of inflammatory bowel disease (IBD); however, the presence of a causal relationship remains elusive. The objective of this study is to investigate the modifications occurring in the cerebral cortex as a result of IBD. A compendium of data extracted from a genome-wide association study (GWAS) involving a maximum of 133,380 European subjects. A series of Mendelian random analyses were applied to exclude heterogeneity and pleiotropy, ensuring the stability of the results. Neither IBDs nor inflammatory cytokines (IL-6/IL-6Rα) were found to have a significant causality with surface area (SA) and thickness (TH) at the global level. At the regional functional brain level, Crohn's disease (CD) significantly decreased the TH of pars orbitalis (β=-0.003mm, Se=0.001mm, p =4.85×10 ). IL-6 was observed to reduce the SA of middle temporal (β=-28.575mm , Se=6.482mm , p =1.04×10 ) and increase the TH of fusiform (β=0.008mm, Se=0.002mm, p =8.86×10 ) and pars opercularis (β=0.009mm, Se=0.002mm, p =2.34×10 ). Furthermore, a causal relationship between IL-6Rα and an increase in the SA of superior frontal (β=21.132mm , Se=5.806mm , p =2.73×10 ) and the TH of supramarginal (β=0.003mm, Se=0.0002mm, p =7.86×10 ). All results passed sensitivity analysis and no heterogeneity and pleiotropy were detected. The correlation between IBD and changes in cerebral cortical structures implies the existence of a gut-brain axis at the organismal level. It is recommended that clinical patients with IBD prioritize long-term management of inflammation, as changes at the organismal level can lead to functional pathologies. Magnetic resonance imaging (MRI) may be considered as an additional screening option for IBD.