Inflammation biomarkers mediate causal inference of the effect of skin microbiota on the risk of allergic diseases.

Abstract

Alterations in skin microbiota composition have been linked to allergic diseases, but the causal relationship remains unclear. To investigate the causal relationship between skin microbiota, allergic diseases, and inflammation biomarkers using Mendelian randomization (MR). We integrated summary statistics from genome-wide association studies (GWAS) of skin microbiota inflammation biomarkers, and seven allergic diseases. Inverse variance weighting (IVW) served as the primary statistical method, with supplementary analyses using MR-Egger regression, weighted median, and Weighted mode. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept test and MR-PRESSO outlier detection, were conducted to validate and stabilize our findings. Two-step MR analyses were performed to identify potential mediating inflammation biomarkers between skin microbiota and allergic diseases.We identified 43 significant causal relationships between the skin microbiota and seven allergic diseases: allergic disease as a whole, asthma (adult, pediatric, allergic), allergic conjunctivitis, allergic rhinitis, atopic dermatitis, allergic urticaria and eczema, which included 20 protective and 23 risk causal relationships, respectively. Mediation analysis showed that specific biomarkers, such as C-C motif chemokine 19 and CD40L receptor levels, Interleukin-18 and TNF-β mediated these associations. This MR study provides robust evidence supporting causal relationships between specific skin microbiota taxa and allergic diseases, as well as potential mediating roles of inflammation biomarkers.