肠道菌群与痤疮之间的因果关系：两样本孟德尔随机化

The Causal Relationship between Gut Microbiota and Acne: A Two-Sample Mendelian Randomization Study

摘要: 背景：越来越多的研究表明肠道菌群与痤疮之间存在一定联系。但由于混杂因素的影响，肠道菌群与痤疮之间是否存在因果关系还未可知。肠道菌群可能通过肠道–皮肤轴增加感染痤疮的风险。方法：我们采用两样本孟德尔随机化(MR)研究来探讨肠道菌群与痤疮之间的关系，使用已发表的全基因组关联研究中的遗传变异作为工具变量。采用逆方差加权法(IVW)、MR Egger回归、加权中位数法和最大似然值法评估两者间因果关系，并进行多重敏感性分析以确保结果的准确。结果：我们确定了Bacteroidaceae与痤疮的因果关系[优势比(OR)：2.25; 95%置信区间(CI)：1.48~3.42；Pivw = 0.0001；错误发现率(FDR) = 0.05]，Bacteroides (OR, 2.25; 95% CI: 1.48~3.42; Pivw = 0.0001; FDR = 0.01)，Allisonella (OR: 1.42; 95% CI: 1.18~1.70; Pivw = 0.0002; FDR = 0.01)。敏感性分析验证了这些因果关系的可靠性。结论：这是第一个确定肠道菌群和痤疮之间因果关系的MR研究。我们的研究揭示了一些肠道菌群是痤疮的危险因素，为痤疮的潜在治疗靶点提供了新的信息，但痤疮与肠道菌群因果关系的内在机制还有待深入研究。

Abstract: Background: Acne is linked to the gut microbiota according to several studies. The association be-tween gut microbiota and acne has yielded conflicting results due to confounding factors, and the causal relationship between them remains undetermined. Intestinal flora may increase the risk of acne infection through the gut-skin axis. Methods: We used a two-sample Mendelian randomization (MR) study to explore the relationship between gut flora and acne, using genetic variation from published genome-wide association studies as an instrumental variable. Inverse variance weighted (IVW), weighted median, MR Egger, and maximum likelihood methods were applied to access caus-al relationships. Several sensitivity analyses were also performed to ensure the accuracy of the re-sults. Results: We found causal associations of Bacteroidaceae [odds ratio (OR), 2.25; 95% confi-dence interval (CI), 1.48~3.42; Pivw = 0.0001; false discovery rate (FDR) = 0.05], Allisonella (OR, 1.42; 95% CI, 1.18~1.70; Pivw = 0.0002; FDR = 0.01), and Bacteroides (OR, 2.25; 95% CI, 1.48~3.42; Pivw = 0.0001; FDR = 0.01) with acne. These results are corrected for false discovery rate. Sensitivity anal-yses validated the associations’ robustness, and reverse MR confirmed that the results were not in-fluenced by the reverse effect. Conclusion: This is the first MR study to determine a causal relation-ship between intestinal flora and acne. Our study revealed some gut microbiotas are risk factors for acne, providing new information on the potential therapeutic targets for acne. The possible connec-tion of the gut skin axis was again confirmed. Further research is needed on the mechanisms behind these relationships.