观察研究的证据表明，皮肤微生物群与皮肤癌有关。然而，皮肤微生物群与皮肤癌之间的因果关系尚未完全阐明。采用双向双样本孟德尔随机化（MR）来确定皮肤微生物群与皮肤癌之间的因果关系。第一项全基因组关联研究在两个德国人群的三个皮肤微环境中鉴定出总共 294 个皮肤微生物类群。三种皮肤癌（恶性黑色素瘤、鳞状细胞癌和基底细胞癌）的摘要数据来自 FinnGen 联盟。此外，敏感性分析检查了水平多效性和异质性，基于微环境的荟萃分析证实了结果的可靠性。我们确定了皮肤微生物群与皮肤癌之间的 65 个名义因果关系和 5 个强因果关系。其中，杆菌类揭示了与恶性黑色素瘤的双向正相关关系。 Betaproteobacteria 类和 Gammaproteobacteria 类分别证明与恶性黑色素瘤和基底细胞癌风险升高存在因果关系。在反向 MR 分析中，恶性黑色素瘤与拟杆菌门丰度较低相关。没有迹象表明仪器变量存在显着异质性，也没有水平多效性的证据。我们的 MR 分析表明皮肤微生物群与皮肤癌之间存在双向因果关系，并有可能为微生物群促进癌发生的机制提供新的视角。版权所有 © 2024朱、刘、王、王、王。

There is evidence from observational studies that skin microbiota is linked to skin cancers. Nevertheless, the causal association between skin microbiota and skin cancers is yet to be fully clarified.A bidirectional two-sample Mendelian randomization (MR) was performed to determine the causal relationship between skin microbiota and skin cancers. A total of 294 skin microbial taxa were identified from the first genome-wide association study across three skin microenvironments of two German population cohorts. Summary data of three skin cancers (malignant melanoma, squamous cell carcinoma, and basal cell carcinoma) were obtained from the FinnGen consortium. Moreover, sensitivity analysis examined horizontal pleiotropy and heterogeneity, and microenvironment-based meta-analysis confirmed the reliability of the results.We identified 65 nominal causalities and 5 strong causal associations between skin microbiota and skin cancers. Among them, the class Bacilli revealed a bidirectional positive relationship with malignant melanoma. The class Betaproteobacteria and class Gammaproteobacteria demonstrated a causal association with an elevated risk of malignant melanoma and basal cell carcinoma, respectively. In the reverse MR analysis, malignant melanoma was associated with a lower abundance of phylum Bacteroidetes. There were no indications of significant heterogeneity in instrumental variables or evidence of horizontal pleiotropy.Our MR analysis indicated bidirectional causal associations between skin microbiota and skin cancers, and had the potential to offer novel perspectives on the mechanistic of microbiota-facilitated carcinogenesis.Copyright © 2024 Zhu, Liu, Wang, Wang and Wang.