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

Abstract

Background: 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.