The Association Between Irritable Bowel Syndrome and Generalized Anxiety Disorder and Influencing Factors: A Mediation Mendelian Randomization Study.

Previous studies showed that irritable bowel syndrome (IBS) and generalized anxiety disorder (GAD) share a common pathogenic mechanism. However, research on links between immune cells, plasma metabolites, inflammatory factors, and gut microbiota and these diseases remains limited. This study aimed to probe causal relationships between these factors and IBS/GAD using Mendelian randomization (MR) analysis. Among factors associated with IBS, 25 gut microbial taxa, 103 plasma metabolites, 7 inflammatory factors, and 42 immune cell characteristics had causal relationships with IBS. Among factors associated with GAD, 35 gut microbial taxa, 72 plasma metabolites, 6 inflammatory factors, and 43 immune cell characteristics had causal links to GAD. IBS was appointed as a risk factor for GAD [odds ratio (OR) = 1.328; p < 0.001]. Mediation analysis showed that IBS acted as a mediator, modulating the effects of 1 immune cell, 1 gut microbiota, and 2 plasma metabolites on GAD. IBS attenuated the protective effects of "Bilophila" on GAD onset (13.30%). This study respectively revealed the potential causal roles of multiple factors in IBS and GAD, as well as the causal relationship between IBS and GAD. Additionally, the mediating role of IBS was unveiled, delivering fresh perspectives on the pathogenesis of IBS and GAD.