肠道菌群与结直肠癌因果关联的双向两样本孟德尔随机化研究

张俏; 周学志; 张德重; 梁书旗; 吴新军; 朱绍辉

doi:10.16766/j.cnki.issn.1674-4152.004036

肠道菌群与结直肠癌因果关联的双向两样本孟德尔随机化研究

doi: 10.16766/j.cnki.issn.1674-4152.004036

1.
新乡医学院第一附属医院胃肠外科减重代谢与疝外科, 河南新乡 453000
2.
新乡医学院医学工程学院, 河南新乡 453000
3.
新乡医学院第一附属医院研究生部

基金项目:

河南省科技攻关计划项目 LHGJ20210536

详细信息

通讯作者:
朱绍辉，E-mail：shaohui912@126.com

中图分类号: R735.3
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- 被引次数: 0
出版历程
- 收稿日期: 2025-01-27
- 网络出版日期: 2025-09-04

Bidirectional two-sample Mendelian randomization study on the causal association between gut microbiota and colorectal cancer

1.
Department of Gastrointestinal Surgery, the First Affiliated Hospital of Xinxiang Medical University, Weight Loss Metabolic and Hernia Surgery, Xinxiang, Henan 453000, China

摘要

摘要: 目的结直肠癌(CRC)的复杂发病机制可能与肠道菌群(GM)存在潜在关联，但现有观察性研究因混杂因素干扰难以明确因果关系。本研究采用双向两样本孟德尔随机化(MR)方法探讨GM与CRC之间的因果关联。方法收集471种GM与CRC的全基因组关联研究(GWAS)数据，筛选出强工具变量(IVs)。采用逆方差加权法(IVW)、加权中位数法(WME)、MR-Egger法、简单模式法和加权模式法评估因果效应，以IVW法为主。进一步使用贝叶斯加权孟德尔随机化(BWMR)法进行分析，并通过OR值及其95% CI展示结果。结合Cochran Q检验、MR-Egger截距检验、MR-PRESSO检验及留一法敏感性分析评估结果的可靠性与稳健性。最后对与CRC有正向因果关联的GM进行反向MR分析。结果 IVW分析显示，Succinivibrionaceae科(OR=0.819，95% CI：0.718~0.934，P=0.003)、Alistipes shahii属(OR=0.731，95% CI：0.573~0.933，P=0.012)、Psychroserpens属(OR=0.643，95% CI：0.492~0.840，P=0.001)、Prevotella buccae属(OR=0.849，95% CI：0.737~0.977，P=0.022)与CRC显著相关。BWMR分析结果与IVW法一致，未发现显著的异质性或水平多效性。反向MR分析未发现CRC与4种GM之间存在显著因果关系(P>0.05)。结论 Succinivibrionaceae科、Alistipes shahii属、Psychroserpens属和Prevotella buccae属的丰度与CRC发病风险呈负相关关系，可能为CRC的保护因素，需进一步研究GM对CRC发病的作用机制。
- 结直肠癌 /
- 肠道菌群 /
- 因果关联 /
- 孟德尔随机化
Abstract: Objective The complex pathogenesis of colorectal cancer (CRC) may be potentially linked to gut microbiota (GM); however, existing observational studies are limited by confounding factors in establishing a clear causal relationship. To explore the causal association between GM and CRC using a bidirectional two-sample Mendelian randomization (MR) method. Methods GWAS data on 471 GM species and CRC were collected, and strong instrumental variables (IVs) were selected. The causal effect was evaluated using the inverse variance weighted method (IVW), weighted median method (WME), MR-Egger method, simple mode method, and weighted mode method, with IVW as the primary approach. Bayesian weighted Mendelian randomization (BWMR) was further used for analysis, and the results were presented with ORs and 95% CIs. The reliability and robustness of the results were assessed through Cochran's Q test, MR-Egger intercept test, MR-PRESSO test, and leave-one-out sensitivity analysis. Finally, a reverse MR analysis was performed for GM species positively associated with CRC. Results IVW analysis showed that the genus Succinivibrionaceae (OR=0.819, 95% CI: 0.718-0.934, P=0.003), Alistipes shahii (OR=0.731, 95% CI: 0.573-0.933, P=0.012), Psychroserpens (OR=0.643, 95% CI: 0.492-0.840, P=0.001), and Prevotella buccae (OR=0.849, 95% CI: 0.737-0.977, P=0.022) were significantly associated with CRC. BWMR results were consistent with the IVW method, and no significant heterogeneity or horizontal pleiotropy was observed. Reverse MR analysis revealed no significant causal relationship between CRC and these four GM species (P>0.05). Conclusion The abundance of Succinivibrionaceae, Alistipes shahii, Psychroserpens, and Prevotella buccae is negatively correlated with the risk of CRC, suggesting that these GM species may be protective factors for CRC. Further research is needed to explore the mechanisms through which GM influences CRC development.
- Colorectal cancer /
- Gut microbiota /
- Causal association /
- Mendelian randomization

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图 1 MR分析的核心假设

Figure 1. Key assumptions of MR analysis

下载: 全尺寸图片幻灯片

图 2 GM与CRC因果关联的正向MR分析

Figure 2. Forward MR analysis of the causal association between GM and CRC

下载: 全尺寸图片幻灯片

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