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肠道微生物群与皮肤黑色素瘤的遗传因果关系:两样本孟德尔随机研究。

Genetic causal relationship between gut microbiota and cutaneous melanoma: a two-sample Mendelian randomization study.

机构信息

Department of Auricular Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Melanoma Res. 2024 Jun 1;34(3):225-233. doi: 10.1097/CMR.0000000000000960. Epub 2024 Mar 11.

Abstract

Currently, numerous studies suggest a potential association between the gut microbiota and the progression of melanoma. Hence, our objective was to examine the genetic impact of the gut microbiota on melanoma through the utilization of the Mendelian randomization (MR) approach. This research employed Bacteroides, Streptococcus, Proteobacteria, and Lachnospiraceae as exposure variables and cutaneous melanoma (CM) as the outcome in a two-sample MR analysis. In this MR research, the primary analytical approach was the random-effects inverse-variance weighting (IVW) model. Complementary methods included weighted median, MR Egger, and basic and weighted models. We assessed both heterogeneity and horizontal pleiotropy in our study, scrutinizing whether the analysis results were affected by any individual SNP. The random-effects IVW outcomes indicated that Streptococcus, Bacteroides, Lachnospiraceae and Proteobacteria had no causal relationship with CM, with odds ratios of 1.001 [95% confidence interval (CI) = 0.998-1.004, P  = 0.444], 0.999 (95% CI = 0.996-1.002, P  = 0.692), 1.001 (95% CI = 0.998-1.003, P  = 0.306), and 0.999 (95% CI = 0.997-1.002, P  = 0.998), respectively. No analyses exhibited heterogeneity, horizontal pleiotropy, or deviations. Our research determined that Bacteroides, Streptococcus, Proteobacteria, and Lachnospiraceae do not induce CM at the genetic level. However, we cannot dismiss the possibility that these four gut microbiotas might influence CM through other mechanisms.

摘要

目前,大量研究表明肠道微生物群与黑色素瘤的进展之间存在潜在关联。因此,我们的目的是通过利用孟德尔随机化(MR)方法来研究肠道微生物群对黑色素瘤的遗传影响。这项研究在两样本 MR 分析中,将拟杆菌属、链球菌属、变形菌门和lachnospiraceae 作为暴露变量,皮肤黑色素瘤(CM)作为结局。在这项 MR 研究中,主要分析方法是随机效应逆方差加权(IVW)模型。补充方法包括加权中位数、MR Egger 以及基本和加权模型。我们在研究中评估了异质性和水平多效性,检查分析结果是否受到任何单个 SNP 的影响。随机效应 IVW 结果表明,链球菌属、拟杆菌属、lachnospiraceae 和变形菌门与 CM 没有因果关系,比值比为 1.001 [95%置信区间(CI)=0.998-1.004,P=0.444]、0.999(95%CI=0.996-1.002,P=0.692)、1.001(95%CI=0.998-1.003,P=0.306)和 0.999(95%CI=0.997-1.002,P=0.998)。没有分析显示存在异质性、水平多效性或偏差。我们的研究确定,拟杆菌属、链球菌属、变形菌门和lachnospiraceae 不会在遗传水平上引起 CM。然而,我们不能排除这四种肠道微生物群可能通过其他机制影响 CM 的可能性。

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