Huang Zirui, Lu Tao, Lin Jiahua, Ding Qike, Li Xiaoting, Lin Lihong
Department of Dermatology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People's Republic of China.
Clin Cosmet Investig Dermatol. 2025 Mar 13;18:579-592. doi: 10.2147/CCID.S496091. eCollection 2025.
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.
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.
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-, and , remained statistically significant (OR = 1.32, 95% CI: 1.16-1.50, = 0.007; OR = 2.25, 95% CI: 1.48-3.42, = 0.026; OR = 1.42, 95% CI: 1.18-1.70, = 0.014; OR = 2.25, 95% CI: 1.48-3.42, = 0.013), with only IL-18R1 significantly associated with eczema (OR = 1.05, 95% CI: 1.03-1.08, = 0.017). Further mediation analysis showed that IL-15RA mediated 11% of the pathway between and eczema, while FGF19 mediated 6% of the pathway between genus and psoriatic arthritis.
These findings provide potential targets for therapeutic interventions in inflammatory skin diseases.
一些研究已经确立了肠道微生物群、炎症蛋白与炎症性皮肤病之间的联系。然而，炎症蛋白在肠-皮肤轴中的中介作用仍不清楚。
炎症蛋白和肠道微生物群的数据来自全基因组关联研究目录（GWAS catalog）和微生物基因组（MiBioGen）联盟，炎症性皮肤病数据由芬兰基因（FinnGen）联盟提供。我们使用全基因组关联研究（GWAS）进行连锁不平衡评分回归（LDSC）以评估遗传相关性，并进行两步孟德尔随机化（MR）分析，以研究循环炎症蛋白作为肠道微生物群与炎症性皮肤病之间的潜在中介。
MR分析确定了38种与炎症性皮肤病相关的肠道微生物群和23种炎症蛋白。经过错误发现率（FDR）校正后，四种肠道微生物分类群，即[具体分类群1]、[具体分类群2]、[具体分类群3]和[具体分类群4]，仍具有统计学意义（比值比=1.32，95%置信区间：1.16-1.50，P=0.007；比值比=2.25，95%置信区间：1.48-3.42，P=0.026；比值比=1.42，95%置信区间：1.18-1.70，P=0.014；比值比=2.25，95%置信区间：1.48-3.42，P=0.013），只有白细胞介素-18受体1（IL-18R1）与湿疹显著相关（比值比=1.05，95%置信区间：1.03-1.08，P=0.017）。进一步的中介分析表明，白细胞介素-15受体α（IL-15RA）介导了[具体分类群1]与湿疹之间11%的通路，而成纤维细胞生长因子19（FGF19）介导了[具体分类属]与银屑病关节炎之间6%的通路。
这些发现为炎症性皮肤病的治疗干预提供了潜在靶点。
