Causal Associations Between Gut Microbiota and Psoriasis: A Mendelian Randomization Study.

Abstract

Previous studies have proposed a possible gut-skin axis, and linked gut microbiota to psoriasis risks. However, there is heterogeneity in existing evidence. Observational research is prone to bias, and it is hard to determine causality. Therefore, this study aims to evaluate possible causal associations between gut microbiota (GM) and psoriasis. With published large-scale GWAS (genome-wide association study) summary datasets, two-sample Mendelian randomization (MR) was performed to sort out possible causal roles of GM in psoriasis and arthropathic psoriasis (PsA). The inverse variance weighted (IVW) method was taken as the primary evaluation of causal association. As complements to the IVW method, we also applied MR-Egger, weighted median. Sensitivity analyses were conducted using Cochrane's Qtest, MR-Egger intercept test, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) global test, and leave-one-out analysis. By primary IVW analysis, we identified nominal protective roles of Bacteroidetes (odds ratio, OR0.81, P = 0.033) and Prevotella9 (OR0.87, P = 0.045) in psoriasis risks. Bacteroidia (OR0.65, P = 0.03), Bacteroidales (OR0.65, P = 0.03), and Ruminococcaceae UCG002 (OR0.81, P = 0.038) are nominally associated with lower risks for PsA. On the other hand, Pasteurellales (OR1.22, P = 0.033), Pasteurellaceae (OR1.22, P = 0.033), Blautia (OR1.46, P = 0.014), Methanobrevibacter (OR1.27, P = 0.026), and Eubacterium fissicatena group (OR1.21, P = 0.028) are nominal risk factors for PsA. Additionally, E.fissicatena group is a possible risk factor for psoriasis (OR1.22, P = 0.00018). After false discovery rate (FDR) correction, E.fissicatena group remains a risk factor for psoriasis (PFDR = 0.03798). We comprehensively evaluated possible causal associations of GM with psoriasis and arthropathic psoriasis, and identified several nominal associations. E.fissicatena group remains a risk factor for psoriasis after FDR correction. Our results offer promising therapeutic targets for psoriasis clinical management.