肠道菌群与2种紫癜性疾病因果关系的孟德尔随机化研究

李文浩; 贾广枝; 张亚; 张炜

doi:10.16766/j.cnki.issn.1674-4152.004165

肠道菌群与2种紫癜性疾病因果关系的孟德尔随机化研究

doi: 10.16766/j.cnki.issn.1674-4152.004165

李文浩^{1, 2},
贾广枝³,
张亚¹,
张炜^1, ,

1.
河南中医药大学附属南阳张仲景医院儿科，河南南阳 473000
2.
河南中医药大学第一附属医院儿科医院河南中医药大学儿科医学院，河南郑州 450000
3.
郑州澍青医学高等专科学校中医系，河南郑州 450000

基金项目:

河南省中医药文化与管理研究项目 TCM2024017

详细信息

通讯作者:
张炜，E-mail：13838966395@163.com

中图分类号: R554.6
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出版历程
- 收稿日期: 2024-08-29
- 网络出版日期: 2025-11-17

Mendelian randomization study on the causal relationship between gut microbiome and two types of purpura diseases

LI Wenhao^{1, 2},
JIA Guangzhi³,
ZHANG Ya¹,
ZHANG Wei^{1
, ,}

1.
Pediatrics Department of Nanyang Zhang Zhongjing Hospital Affiliated to Henan University of Chinese Medicine, Nanyang, Henan 473000, China

摘要

摘要: 目的通过孟德尔随机化(MR)研究方法分析肠道菌群与过敏性紫癜(HSP)及免疫性血小板减少症(ITP)的因果关系。方法利用公开的全基因组关联研究数据库获取暴露因素肠道菌群与结局变量HSP/ITP数据集，采用逆方差加权(IVW)、MR Egger、加权中位数、简单众数、加权众数等方法进行MR分析。以OR值评估肠道菌群与HSP/ITP的因果关系，并进行Cochran ' s Q检验、MR Egger截距检验等敏感性分析来评判结果的稳健性。结果 IVW分析显示，DefluviitaleaceaeUCG011 (OR=2.211, 95% CI: 1.138~4.296, P=0.019)增加了HSP发病风险; Sutterella(OR=0.483, 95% CI: 0.256~0.914, P=0.025)降低了HSP发病风险。Lactococcus(OR=2.684, 95% CI: 1.335~5.397, P=0.006)、Tyzzerella3(OR=2.602，95% CI: 1.344~5.038, P=0.005)增加了ITP发病风险; Romboutsia(OR=0.232，95% CI: 0.077~0.704，P=0.010)、Parabacteroides(OR=0.050，95% CI: 0.003~0.898，P=0.042)降低了ITP发病风险。敏感性分析均提示结果稳定，不存在异质性和多效性。结论肠道菌群与HSP/ITP发生风险可能存在因果关系，通过调节肠道菌群可能有助于HSP/ITP的预防和治疗。
- 过敏性紫癜 /
- 免疫性血小板减少症 /
- 孟德尔随机化 /
- 肠道菌群
Abstract: Objective To analyze the causal relationship between intestinal flora and Henoch-Schönlein purpura (HSP) and idiopathic thrombocytopenic purpura (ITP) by means of Mendelian randomization (MR). Methods The published genome-wide association study database was utilized to obtain the HSP/ITP data set of exposure factor intestinal flora and outcome variables. Inverse variance weighting (IVW), MR Egger, weighted median, simple mode and weighted mode were utilized for MR Analysis. The OR value was utilized to evaluate the causal relationship between intestinal flora and HSP/ITP, and sensitivity analysis, including Cochran ' s Q test and the MR Egger intercept test was conducted to evaluate the robustness of the results. Results The IVW analysis demonstrated that DefluviitaleaceaeUCG011 (OR=2.211, 95% CI: 1.138-4.296, P=0.019) was associated with an elevated risk of HSP. Sutterella (OR=0.483, 95% CI: 0.256-0.914, P=0.025) was associated with a reduced the risk of HSP. Lactococcus (OR=2.684, 95% CI: 1.335-5.397, P=0.006) and Tyzzerella3 (OR=2.602, 95% CI: 1.344-5.038, P=0.005) were found to be significant risk factors for ITP. Romboutsia (OR=0.232, 95% CI: 0.077-0.704, P=0.010) and Parabacteroides (OR=0.050, 95% CI: 0.003-0.898, P=0.042) have been shown to reduce the risk of ITP. Conclusion The present study hypothesizes that there is a causal relationship between the gut microbiome and the risk of HSP/ITP, and modulating the gut microbiome may be beneficial in the prevention and treatment of HSP/ITP.
- Henoch-Schonlein purpura /
- Idiopathic thrombocytopenic purpura /
- Mendelian randomization /
- Gut microbiota

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图 1 留一法敏感性分析结果

注：A为Defluviitaleaceae UCG011属; B为萨特氏菌属; C为乳球菌属; D为泰氏菌属3群; E为罗姆布茨菌属; F为副拟杆菌属。

Figure 1. Leave one out sensitivity analysis results

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表 1 肠道菌群与HSP/ITP风险因果关系的MR分析

Table 1. MR Analysis of causal relationship between gut microbiota and HSP/ITP risk

暴露	结局	检验方法	P值	OR(95% CI)	异质性检验P值	多效性检验P值
DefluviitaleaceaeUCG011	过敏性紫癜	MR Egger回归	0.039	17.229(1.899~156.300)	0.556	0.099
		加权中位数法	0.084	2.178(0.900~5.272)
		逆方差加权法	0.019	2.211(1.138~4.296)	0.304
		简单众数法	0.366	2.030(0.477~8.632)
		加权众数法	0.359	1.923(0.514~7.193)
萨特氏菌属		MR Egger回归	0.978	0.961(0.060~15.273)	0.946	0.628
		加权中位数法	0.070	0.467(0.205~1.063)
		逆方差加权法	0.025	0.483(0.256~0.914)	0.961
		简单众数法	0.174	0.352(0.086~1.439)
		加权众数法	0.237	0.437(0.120~1.599)
乳球菌属	免疫性血小板减少症	MR Egger回归	0.982	0.966(0.050~18.783)	0.183	0.512
		加权中位数法	0.043	2.315(1.026~5.224)
		逆方差加权法	0.006	2.684(1.335~5.397)	0.215
		简单众数法	0.188	2.197(0.764~6.322)
		加权众数法	0.129	2.282(0.891~5.844)
泰氏菌属3群		MR Egger回归	0.775	1.770(0.040~78.036)	0.977	0.844
		加权中位数法	0.030	2.572(1.094~6.045)
		逆方差加权法	0.005	2.602(1.344~5.038)	0.989
		简单众数法	0.179	2.244(0.758~6.647)
		加权众数法	0.146	2.357(0.820~6.775)
罗姆布茨菌属		MR Egger回归	0.154	0.059(0.002~2.083)	0.585	0.449
		加权中位数法	0.021	0.162(0.035~0.761)
		逆方差加权法	0.010	0.232(0.077~0.704)	0.616
		简单众数法	0.109	0.154(0.019~1.240)
		加权众数法	0.083	0.174(0.029~1.035)
副拟杆菌属		MR Egger回归	0.510	0.000(0.000~51 938.225)	0.188	0.610
		加权中位数法	0.074	0.057(0.002~1.324)
		逆方差加权法	0.042	0.050(0.003~0.898)	0.274
		简单众数法	0.218	0.008(0.000~1.662)
		加权众数法	0.441	0.204(0.008~5.334)

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