探索肠道微生物群、炎症细胞因子和炎症性皮肤病之间的因果关系：一项孟德尔随机研究。

IF 1.9 4区医学 Q3 DERMATOLOGY

Clinical, Cosmetic and Investigational Dermatology Pub Date : 2025-03-13 eCollection Date: 2025-01-01 DOI:10.2147/CCID.S496091

Zirui Huang, Tao Lu, Jiahua Lin, Qike Ding, Xiaoting Li, Lihong Lin

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引用次数: 0

摘要

背景：一些研究已经建立了肠道微生物群、炎症蛋白和炎症性皮肤病之间的联系。然而，炎症蛋白在肠-皮肤轴中的介导作用尚不清楚。方法：炎症蛋白和肠道菌群数据来自GWAS目录和MiBioGen联盟，炎症性皮肤病数据由FinnGen联盟提供。利用全基因组关联研究（GWAS），我们进行了连锁不平衡评分回归（LDSC）来评估遗传相关性，并进行了两步孟德尔随机化（MR）分析，以研究循环炎症蛋白作为肠道微生物群和炎症性皮肤病之间的潜在介质。结果：磁共振分析鉴定出38种肠道微生物群和23种与炎症性皮肤病相关的炎症蛋白。在错误发现率（FDR）校正后，4个肠道菌群分类——裂裂真杆菌、拟杆菌科、蒜香菌和拟杆菌，仍然具有统计学意义(OR = 1.32, 95% CI: 1.16-1.50，校正后P = 0.007；OR = 2.25, 95% CI: 1.48 ~ 3.42，调整后P = 0.026；OR = 1.42, 95% CI: 1.18-1.70，校正P = 0.014；OR = 2.25, 95% CI: 1.48 ~ 3.42，校正P = 0.013)，只有IL-18R1与湿疹显著相关（OR = 1.05, 95% CI: 1.03 ~ 1.08，校正P = 0.017）。进一步的中介分析表明，IL-15RA介导了细络科与湿疹之间11%的通路，而FGF19介导了LachnospiraceaeUCG001属与银屑病关节炎之间6%的通路。结论：这些发现为炎症性皮肤病的治疗干预提供了潜在的靶点。

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

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.

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来源期刊

Clinical, Cosmetic and Investigational Dermatology Medicine-Dermatology

CiteScore

2.80

自引率

4.30%

发文量

353

审稿时长

16 weeks

期刊介绍： Clinical, Cosmetic and Investigational Dermatology is an international, peer-reviewed, open access journal that focuses on the latest clinical and experimental research in all aspects of skin disease and cosmetic interventions. Normal and pathological processes in skin development and aging, their modification and treatment, as well as basic research into histology of dermal and dermal structures that provide clinical insights and potential treatment options are key topics for the journal. Patient satisfaction, preference, quality of life, compliance, persistence and their role in developing new management options to optimize outcomes for target conditions constitute major areas of interest. The journal is characterized by the rapid reporting of clinical studies, reviews and original research in skin research and skin care. All areas of dermatology will be covered; contributions will be welcomed from all clinicians and basic science researchers globally.