Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Front Immunol. 2023 Sep 27;14:1231848. doi: 10.3389/fimmu.2023.1231848. eCollection 2023.
BACKGROUND: Observational studies have shown that gut microbiota is closely associated with inflammatory dermatoses such as psoriasis, rosacea, and atopic dermatitis (AD). However, the causal relationship between gut microbiota and inflammatory dermatosis remains unclear. METHODS: Based on Maximum Likelihood (ML), MR-Egger regression, Inverse Variance Weighted (IVW), MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), Weighted Mode, and Weighted Median Estimator (WME) methods, we performed a bidirectional two-sample Mendelian randomization (MR) analysis to explore the causal relationship between gut microbiota and inflammatory dermatosis. The genome-wide association study (GWAS) summary data of gut microbiota came from the MiBioGen consortium, while the GWAS summary data of inflammatory dermatosis (including psoriasis, AD, rosacea, vitiligo, acne, and eczema) came from the FinnGen consortium and IEU Open GWAS project. Cochran's IVW Q test tested the heterogeneity among instrumental variables (IVs). The horizontal pleiotropy was tested by MR-Egger regression intercept analysis and MR-PRESSO analysis. RESULTS: Eventually, the results indicated that 5, 16, 17, 11, 15, and 12 gut microbiota had significant causal effects on psoriasis, rosacea, AD, vitiligo, acne, and eczema, respectively, including 42 protective and 34 risk causal relationships. Especially, Lactobacilli and Bifidobacteria at the Family and Genus Level, as common probiotics, were identified as protective factors for the corresponding inflammatory dermatoses. The results of reverse MR analysis suggested a bidirectional causal effect between AD and genus Eubacterium brachy group, vitiligo and genus Ruminococcaceae UCG004. The causal relationship between gut microbiota and psoriasis, rosacea, acne, and eczema is unidirectional. There was no significant heterogeneity among these IVs. In conclusion, this bidirectional two-sample MR study identified 76 causal relationships between the gut microbiome and six inflammatory dermatoses, which may be helpful for the clinical prevention and treatment of inflammatory dermatoses.
背景：观察性研究表明，肠道微生物群与炎症性皮肤病如银屑病、酒渣鼻和特应性皮炎（AD）密切相关。然而，肠道微生物群与炎症性皮肤病之间的因果关系仍不清楚。
方法：基于最大似然（ML）、MR-Egger 回归、逆方差加权（IVW）、MR 偏残差和异常值（MR-PRESSO）、加权模式和加权中位数估计器（WME）方法，我们进行了双向两样本 Mendelian 随机化（MR）分析，以探讨肠道微生物群与炎症性皮肤病之间的因果关系。肠道微生物群的全基因组关联研究（GWAS）汇总数据来自 MiBioGen 联盟，而炎症性皮肤病（包括银屑病、AD、酒渣鼻、白癜风、痤疮和湿疹）的 GWAS 汇总数据来自 FinnGen 联盟和 IEU Open GWAS 项目。Cochran 的 IVW Q 检验检验了工具变量（IVs）之间的异质性。MR-Egger 回归截距分析和 MR-PRESSO 分析检验了水平偏倚。
结果：最终，结果表明，5、16、17、11、15 和 12 种肠道微生物群分别对银屑病、酒渣鼻、AD、白癜风、痤疮和湿疹有显著的因果影响，包括 42 种保护和 34 种风险因果关系。特别是，属水平的乳杆菌和双歧杆菌作为常见的益生菌，被鉴定为相应炎症性皮肤病的保护因素。反向 MR 分析的结果表明，AD 和属真细菌短双歧杆菌之间以及白癜风和属瘤胃球菌科 UCG004 之间存在双向因果关系。肠道微生物群与银屑病、酒渣鼻、痤疮和湿疹之间的因果关系是单向的。这些 IVs 之间没有显著的异质性。总之，这项双向两样本 MR 研究确定了 76 种肠道微生物群与六种炎症性皮肤病之间的因果关系，这可能有助于炎症性皮肤病的临床预防和治疗。
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