遗传学视角下皮肤菌群与痤疮的因果关联：两样本孟德尔随机化研究

The Causal Relationship between Skin Microbiota and Acne from a Genetic Perspective: A Two-Sample Mendelian Randomization Study

摘要: 背景：皮肤微生物群(SM)与痤疮发展风险之间的因果关系仍不确定。通过进行一项单变量和多变量孟德尔随机化(MR)研究，以调查它们是否与痤疮有因果关系。方法：进行双样本MR分析，以调查SM和痤疮之间的潜在因果关系。MR分析主要采用逆方差加权法，以及加权中位数法、MR-Egger回归和加权模式。此外，采用Cochran’s Q、MR-Egger截距、MR-PRESSO和留一分析检验MR分析结果的可靠性。结果：逆方差加权法显示微球菌属、ASV004、ASV008和ASV070是痤疮的保护因素。相反，杆菌类和葡萄球菌属是痤疮的危险因素。此外，金黄杆菌属、不动杆菌属、拟杆菌属、ASV001、ASV003和ASV016与痤疮有潜在关联。此外，在门、目和科水平上，没有发现SM和痤疮之间的因果关系。结论：双样本MR分析揭示了SM和痤疮之间的因果关系，可能为未来SM介导的痤疮发病机制的机制和临床研究提供有价值的新见解。

Abstract: Background: The causal relationship between skin microbiota (SM) and the risk of acne development remains uncertain. We performed a univariate and multivariate Mendelian randomization (MR) study to investigate whether they are causally related to acne. Methods: We performed two-sample MR analysis to investigate the potential causal relationship between SM and acne. The MR analysis was performed primarily using the inverse variance weighting method, and secondarily using the weighted median method, MR-Egger regression, and weighted mode. In addition, the reliability of the MR analysis results was tested using Cochran’s Q, MR-Egger intercept, MR-PRESSO, and leave-one-out analysis. Results: The inverse variance weighting method showed that Micrococcus, ASV004, ASV008, and ASV070 were protective factors for acne. In contrast, Bacillus and Staphylococcus were risk factors for acne. In addition, Chryseobacterium, Acinetobacter, Bacteroides, ASV001, ASV003, and ASV016 were suggestive associations with acne. Furthermore, no causal relationship between SM and acne was found at the phylum, order, and family levels. Conclusion: Our MR analysis revealed a causal relationship between SM and acne, which may provide valuable new insights into the mechanistic and clinical studies of SM-mediated acne pathogenesis in the future.