肠道微生物群在血栓闭塞性脉管炎中的作用：队列研究和孟德尔随机化研究

The Role of Gut Microbiota in Thromboangiitis Obliterans: Cohort and Mendelian Randomization Study.

作者信息

Sheng Chang, Huang Weihua, Liao Mingmei, Yang Pu

机构信息

Department of Vascular Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.

Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital, Central South University, Changsha 410078, China.

出版信息

Biomedicines. 2024 Jul 1;12(7):1459. doi: 10.3390/biomedicines12071459.

BACKGROUND AND AIMS

Thromboangiitis obliterans (TAO), also known as Buerger's disease, is a rare vasculitis. Observational epidemiology studies have suggested a relationship between the gut microbiota and TAO. However, due to confounding factors and reverse causality, the causal relationship remains unclear. Based on the assumption of their association, this study sought specific gut microbiota causally linked to TAO.

METHODS

The case-control study was conducted at the Xiangya Hospital of Central South University from November 2022 to January 2023 including twelve TAO patients and nine healthy controls. We conducted a Mendelian randomization (MR) study using summary statistics from a genome-wide association study (GWAS) of gut microbiota and TAO. Considering the scale and accessibility of the data, the MiBioGen consortium served as the exposure, whereas the FinnGen consortium GWAS study served as the outcome. Finally, we compared the results of the MR with those of the case-control studies.

RESULTS

The inverse variance weighted (IVW) (OR = 0.119, 95% CI: 0.021-0.688, = 0.017) and maximum likelihood (ML) (OR = 0.121, 95% CI: 0.020-0.742, = 0.022) estimates suggest that has a suggestive protective effect on TAO while the IVW (OR = 5.383, 95% CI: 1.128-25.693, = 0.035) and ML (OR = 5.658, 95% CI: 1.142-28.021, = 0.034) estimates suggest that () has a suggestive risk effect on TAO, and the ML (OR = 0.055, 95% CI: 0.004-0.755, = 0.030) estimates suggest that has a suggestive protective effect on TAO. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. The results of the case-control study showed that the TAO had a lower relative abundance of ( = 0.015) and ( = 0.048), and a higher relative abundance of () ( = 0.029) than the healthy controls. These results were consistent with the MR analysis.

CONCLUSIONS

Our study demonstrates that , , and () are causally related to TAO, suggesting their potential significance for the prevention and treatment of TAO.

背景与目的

血栓闭塞性脉管炎（TAO），又称伯格氏病，是一种罕见的血管炎。观察性流行病学研究表明肠道微生物群与TAO之间存在关联。然而，由于混杂因素和反向因果关系，因果关系仍不明确。基于它们之间关联的假设，本研究寻找与TAO有因果关系的特定肠道微生物群。

方法

2022年11月至2023年1月在中南大学湘雅医院进行了病例对照研究，包括12例TAO患者和9名健康对照。我们使用来自肠道微生物群和TAO的全基因组关联研究（GWAS）的汇总统计数据进行了孟德尔随机化（MR）研究。考虑到数据的规模和可及性，MiBioGen联盟作为暴露因素，而芬兰基因组联盟GWAS研究作为结果。最后，我们将MR的结果与病例对照研究的结果进行了比较。

结果

逆方差加权（IVW）（比值比=0.119，95%置信区间：0.021 - 0.688，P=0.017）和最大似然（ML）（比值比=0.121，95%置信区间：0.020 - 0.742，P=0.022）估计表明，[具体微生物名称1]对TAO有提示性保护作用，而IVW（比值比=5.383，95%置信区间：1.128 - 25.693，P=0.035）和ML（比值比=5.658，95%置信区间：1.142 - 28.021，P=0.034）估计表明，[具体微生物名称2]（[微生物具体描述2]）对TAO有提示性风险作用，且ML（比值比=0.055，95%置信区间：0.004 - 0.755，P=0.030）估计表明，[具体微生物名称3]对TAO有提示性保护作用。未发现工具变量的显著异质性或水平多效性。病例对照研究结果显示，与健康对照相比，TAO患者中[具体微生物名称1]的相对丰度较低（P=0.015），[具体微生物名称4]的相对丰度较低（P=0.048），而[具体微生物名称2]（[微生物具体描述2]）的相对丰度较高（P=0.029）。这些结果与MR分析一致。