Causal relationship between gut microbiota, structural connectivity, and psoriasis: A Mendelian randomization

Background Previous studies have demonstrated a causal relationship between gut microbiota/structural connectivity and psoriasis. However, it is not clear whether structural connectivity act as mediator in the pathway from gut microbiota to psoriasis. Methods Based on genome-wide association studies (GWAS), we performed two-step MR-analysis in order to examine the role of structural connectivity (N = 26,333) as potential mediators between gut microbiota (N = 13,266) and psoriasis (N = 15,967). Summary statistics for gut microbiota were sourced from MiBioGen consortium, while the data of structural connectivity and psoriasis came from the GWAS catalog. Results Through MR analysis, we identified 2 gut microbiota and 15 inflammatory proteins related to psoriasis such as genus Coprococcus3 and LH Limbic to caudate (OR = 1.33, 95% CI: 1.00–1.76, P  = 0.048; OR = 0.70, 95% CI: 0.56–0.86, P  = 0.001). After MVMR analysis, LH Limbic to caudate remained significant in relation to a decreased risk of psoriasis ( P  = 0.0005) while the association was no longer significant between genus Coprococcus3 and psoriasis ( P  = 0.121). The mediating effect was calculated as 0.047 (OR = 1.049, 95% CI: 1.006–1.109) accounting for 16.6% of the total effect. Conclusion Our study provides genetic evidence that in the pathway from gut microbiota to psoriasis, structural connectivity act as mediators.