Inflammatory bowel diseases, interleukin-6 and interleukin-6 receptor subunit alpha in causal association with cerebral cortical structure: a Mendelian randomization analysis
Chunlong Liu, Shijie Zhu, Jian Zhang, Kuiwu Ren, Kangkang Li, Jiangtao Yu
Abstract
Background 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. Methods 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. 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 ivw =4.85×10 -4 ). IL-6 was observed to reduce the SA of middle temporal (β=-28.575mm 2 , Se=6.482mm 2 , p ivw =1.04×10 -5 ) and increase the TH of fusiform (β=0.008mm, Se=0.002mm, p ivw =8.86×10 -5 ) and pars opercularis (β=0.009mm, Se=0.002mm, p ivw =2.34×10 -4 ). Furthermore, a causal relationship between IL-6Rα and an increase in the SA of superior frontal (β=21.132mm 2 , Se=5.806mm 2 , p ivw =2.73×10 -4 ) and the TH of supramarginal (β=0.003mm, Se=0.0002mm, p ivw =7.86×10 -37 ). All results passed sensitivity analysis and no heterogeneity and pleiotropy were detected. Conclusion 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.