Psoriasis is a chronic, systemic autoimmune disorder characterized by abnormal skin cell proliferation and inflammation, affecting millions worldwide. Recent research has highlighted the role of the skin microbiota in regulating immune responses, sparking interest in its potential link to psoriasis. This study investigates the causal relationship between skin microbiota and psoriasis using Mendelian Randomization (MR), a technique that leverages genetic instrumental variables (IVs) to infer causality from observational data.
Methods:
- Data Sources: Psoriasis summary statistics were sourced from FinnGen R10 and the UK Biobank (UKB). Skin microbiota data were obtained from two German cohorts: KORA FF4 and PopGen, involving 1,656 skin samples.
- MR Analysis: A total of 449 single nucleotide polymorphisms (SNPs) were used as IVs for 53 bacterial genera. The study employed five MR methods to test for causal relationships:
- Inverse Variance Weighted (IVW)
- Maximum Likelihood (Maxlik)
- Robust Adjusted Profile Score (RAPS)
- Weighted Median (WM)
- MR-Egger Regression
Key Findings:
- Instrumental Variables: The 449 SNPs used as IVs for 53 bacterial genera had F-statistics ranging from 20.18 to 42.44, confirming strong IVs and ruling out weak instrument bias.
- Association with Psoriasis:
- Protective Effect of Bacteroides: The genus Bacteroides, particularly from the moist antecubital fossa region, was significantly associated with a reduced risk of psoriasis and related disorders. The IVW method yielded an odds ratio (OR) of 0.914 (95% CI: 0.869โ0.961; P < 0.001) for psoriasis, 0.918 (95% CI: 0.872โ0.967; P = 0.001) for psoriasis vulgaris, and 0.915 (95% CI: 0.875โ0.957; P < 0.001) for psoriasis and related disorders.
- Consistency Across Methods: Results were consistent across different MR methods, confirming a robust protective effect of Bacteroides.
- Mechanistic Insights: Bacteroides is likely to exert a protective effect by modulating immune responses and producing short-chain fatty acids (SCFAs) such as butyrate, which reduce inflammatory cytokine production.
- Robustness and Validation: No significant heterogeneity was detected, and MR-Egger regression did not show evidence of horizontal pleiotropy. The leave-one-out analysis confirmed that the findings were not influenced by any single SNP.
Conclusion:
This Mendelian Randomization study provides novel genetic evidence supporting a protective role of the skin microbiota genus Bacteroides in psoriasis. By addressing the causality question more rigorously than previous epidemiological studies, the research suggests that Bacteroides could be a promising target for psoriasis prevention or treatment.
Future research should explore the mechanisms through which Bacteroides influences psoriasis and evaluate the potential for microbiota-based therapies in clinical settings.
Link to the study: https://tinyurl.com/3kwjmh6x
