Irritable Bowel Syndrome is Associated with Brain Health by Neuroimaging, Behavioral, Biochemical, and Genetic Analyses

BACKGROUND:Irritable bowel syndrome (IBS) interacts with psychopathology in a complex way, yet little is known about the underlying brain, biochemical and genetic mechanisms. METHODS:To clarify the phenotypic and genetic associations between IBS and brain health, we performed a comprehensive retrospective cohort study on a large population. Our study included 171,104 participants from the UK Biobank who underwent a thorough assessment of the IBS syndrome, with the majority also providing neuroimaging, behavioral, biochemical, and genetic information. Multistage linked analyses were conducted, including phenome-wide association analysis, polygenic risk score calculation, and two-sample Mendelian Randomization (MR) analysis. RESULTS:The phenome-wide association analysis showed that IBS is linked to brain health problems, including anxiety and depression, and poor cognitive performance. Significantly lower brain volumes associated with more severe IBS were found in key areas related to emotional regulation and higher-order cognition, including the medial orbitofrontal cortex/ventromedial prefrontal cortex, anterior insula, anterior and mid-cingulate cortex, dorsolateral prefrontal cortex, and hippocampus. Higher triglycerides, lower high-intensity lipoprotein, and lower platelets were also related (p < 1×10-10) to more severe IBS. Finally, MR analyses demonstrated potential causal relationships between IBS and brain health, and indicated the possible mediating effects of dislipidemia and inflammation. CONCLUSIONS:This study, for the first time, provides a comprehensive understanding of the relationship between IBS and brain health phenotypes, integrating perspectives from neuroimaging, behavioral performance, biochemical factors and genetics, which is of great significance for clinical application of brain health impairments in patients with IBS.