肠道微生物组对 HIV 感染的因果效应：两样本孟德尔随机化分析。

Causal effects of gut microbiome on HIV infection: a two-sample mendelian randomization analysis.

机构信息

College of Public Health, Chongqing Medical University, Chongqing, China.

出版信息

BMC Infect Dis. 2024 Mar 4;24(1):280. doi: 10.1186/s12879-024-09176-5.

DOI:10.1186/s12879-024-09176-5

PMID:38438963

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10913272/

Abstract

BACKGROUND

The causal association between gut microbiome and HIV infection remains to be elucidated. We conducted a two-sample mendelian randomization analysis to estimate the causality between gut microbiome and HIV infection.

METHODS

Publicly released genome-wide association studies summary data were collected to perform the mendelian analysis. The GWAS summary data of gut microbiome was retrieved from the MiBioGen consortium, which contains 18 340 samples from 24 cohorts. GWAS summary data of HIV infection was collected from the R5 release of FinnGen consortium, including 357 HIV infected cases and 218 435 controls. The SNPs were selected as instrumental variables according to our selection rules. And SNPs with a F-statistics less than ten were regarded as weak instrumental variables and excluded. Mendelian randomization analysis was conducted by five methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode. The Cochran's Q test and MR-Egger intercept test were performed to identify heterogeneity and pleiotropy. Leave-one-out analysis were used to test the sensitivity of the results.

RESULTS

Fifteen gut microbiota taxa showed causal effects on HIV infection according to the MR methods. Four taxa were observed to increase the risk of HIV infection, including Ruminococcaceae (OR: 2.468[1.043, 5.842], P: 0.039), Ruminococcaceae UCG005 (OR: 2.051[1.048, 4.011], P: 0.036), Subdoligranulum (OR: 3.957[1.762, 8.887], P < 0.001) and Victivallis (OR: 1.605[1.012, 2.547], P=0.044). Erysipelotrichaceae was protective factor of HIV infection (OR: 0.278[0.106, 0.731], P < 0.001) and Methanobrevibacter was also found to be associated with reduced risk of HIV infection (OR: 0.509[0.265, 0.980], P=0.043). Horizontal pleiotropy was found for Fusicatenibacter (P<0.05) according to the MR-Egger regression intercept analysis. No heterogeneity was detected.

CONCLUSION

Our results demonstrate significant causal effects of gut microbiome on HIV infection. These findings facilitate future studies to develop better strategies for HIV prophylaxis through gut microbiome regulation. Further explorations are also warranted to dissect the mechanism of how gut microbiome affects HIV susceptibility.

摘要

背景

肠道微生物组与 HIV 感染之间的因果关系仍有待阐明。我们进行了两样本孟德尔随机化分析，以估计肠道微生物组与 HIV 感染之间的因果关系。

方法

收集了公开发布的全基因组关联研究汇总数据，以进行孟德尔分析。肠道微生物组的 GWAS 汇总数据来自 MiBioGen 联盟，该联盟包含 24 个队列的 18340 个样本。HIV 感染的 GWAS 汇总数据来自 FinnGen 联盟的 R5 版本，包括 357 例 HIV 感染者和 218435 例对照。根据我们的选择规则，将 SNP 选为工具变量。并且，将 F-统计量小于 10 的 SNP 视为弱工具变量并排除。通过五种方法（包括逆方差加权法[IVW]、MR-Egger、加权中位数、加权模式和简单模式）进行孟德尔随机化分析。使用 Cochran's Q 检验和 MR-Egger 截距检验来识别异质性和多效性。采用单样本分析来检验结果的敏感性。

结果

根据 MR 方法，有 15 种肠道微生物群与 HIV 感染呈因果关系。有四种肠道微生物群被观察到会增加 HIV 感染的风险，包括 Ruminococcaceae（OR：2.468[1.043，5.842]，P：0.039）、Ruminococcaceae UCG005（OR：2.051[1.048，4.011]，P：0.036）、Subdoligranulum（OR：3.957[1.762，8.887]，P<0.001）和 Victivallis（OR：1.605[1.012，2.547]，P=0.044）。Erysipelotrichaceae 是 HIV 感染的保护因素（OR：0.278[0.106，0.731]，P<0.001），Methanobrevibacter 也与 HIV 感染风险降低相关（OR：0.509[0.265，0.980]，P=0.043）。根据 MR-Egger 回归截距分析，发现 Fusicatenibacter 存在水平多效性（P<0.05）。未检测到异质性。