Exploring Causal Relationships Between Gut Microbiota, Inflammatory Cytokines, and Inflammatory Dermatoses: A Mendelian Randomization Study

Zirui Huang, Tao Lu, Jiahua Lin, Qike Ding, Xiaoting Li, Lihong Lin Department of Dermatology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of ChinaCorrespondence: Tao Lu, Email [email protected]: Some studies have established a link between gut microbiota, inflammatory proteins, and inflammatory dermatoses. However, the mediating role of inflammatory proteins in the gut-skin axis remains unclear.Methods: Data on inflammatory proteins and gut microbiota were drawn from the GWAS catalog and MiBioGen consortium, with inflammatory skin disease data provided by the FinnGen consortium. Using genome-wide association studies (GWAS), we performed linkage disequilibrium score regression (LDSC) to assess genetic correlations and conducted a two-step Mendelian Randomization (MR) analysis to investigate circulating inflammatory proteins as potential mediators between gut microbiota and inflammatory dermatoses.Results: MR analysis identified 38 gut microbiota and 23 inflammatory proteins associated with inflammatory skin diseases. After false discovery rate (FDR) correction, four gut microbiota taxa—Eubacterium fissicatena, Bacteroidaceae, Allisonella, and Bacteroides, remained statistically significant (OR = 1.32, 95% CI: 1.16– 1.50, adjusted P = 0.007; OR = 2.25, 95% CI: 1.48– 3.42, adjusted P = 0.026; OR = 1.42, 95% CI: 1.18– 1.70, adjusted P = 0.014; OR = 2.25, 95% CI: 1.48– 3.42, adjusted P = 0.013), with only IL-18R1 significantly associated with eczema (OR = 1.05, 95% CI: 1.03– 1.08, adjusted P = 0.017). Further mediation analysis showed that IL-15RA mediated 11% of the pathway between Veillonellaceae and eczema, while FGF19 mediated 6% of the pathway between genus LachnospiraceaeUCG001 and psoriatic arthritis.Conclusion: These findings provide potential targets for therapeutic interventions in inflammatory skin diseases.Keywords: gut microbiota, inflammatory dermatoses, Mendelian randomization, inflammatory proteins, genetic correlation