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中华普通外科学文献(电子版) ›› 2025, Vol. 19 ›› Issue (03) : 163 -168. doi: 10.3877/cma.j.issn.1674-0793.2025.03.003

论著

肠道微生物群、血液代谢物和胃癌的因果关系:东亚人群中介孟德尔随机化研究
王思卓1, 段晓鑫1, 陈隆1, 董胜利2,()   
  1. 1. 030001 太原,山西医科大学
    2. 030001 太原,山西医科大学第二医院普通外科
  • 收稿日期:2025-01-23 出版日期:2025-06-01
  • 通信作者: 董胜利

Causal effect of gut microbiome, blood metabolites and gastric cancer: A mediated Mendelian randomization study in East Asian populations

Sizhuo Wang1, Xiaoxin Duan1, Long Chen1, Shengli Dong2,()   

  1. 1. Shanxi Medical University, Taiyuan 030001, China
    2. Department of General Surgery, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China
  • Received:2025-01-23 Published:2025-06-01
  • Corresponding author: Shengli Dong
引用本文:

王思卓, 段晓鑫, 陈隆, 董胜利. 肠道微生物群、血液代谢物和胃癌的因果关系:东亚人群中介孟德尔随机化研究[J/OL]. 中华普通外科学文献(电子版), 2025, 19(03): 163-168.

Sizhuo Wang, Xiaoxin Duan, Long Chen, Shengli Dong. Causal effect of gut microbiome, blood metabolites and gastric cancer: A mediated Mendelian randomization study in East Asian populations[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2025, 19(03): 163-168.

目的

通过中介孟德尔随机化(MR)分析探讨肠道微生物群、血液代谢物和胃癌在东亚人群中的因果效应。

方法

从公开的全基因组关联研究(GWAS)数据库中获取500 种肠道微生物组、112 种血液代谢物、7 921 例胃癌患者和159 201 例对照的汇总统计数据进行双样本MR 分析。采用两步法量化血液代谢物介导的肠道菌群对胃癌影响的比例。逆方差加权法(IVW)为主要的效应估计方法,同时使用MR-Egger、加权中位数法、简单模式、加权模式作为补充,并利用敏感性分析来验证MR 结果的可靠性。

结果

14 种肠道微生物与东亚人群胃癌风险明显相关,其中8 种被确定为风险因素。通过采用两步MR 分析,发现3 条代谢功能通路(鼠李糖降解、精氨酸降解途径Ⅰ和非氧化分支磷酸戊糖途径)通过两种血液代谢物(氢化可的松和维生素K)的中介作用,与东亚人群胃癌风险存在因果关系,其中维生素K 的中介作用比例最高,在精氨酸降解途径Ⅰ和非氧化分支磷酸戊糖途径中分别为13.50%和16.20%。

结论

以氢化可的松和维生素K 为代表的血液代谢物可能介导肠道微生物群对胃癌的致病过程,为胃癌的诊断、治疗和早期预防提供了新的思路。

Objective

To explore the causal link among gut microbiome, blood metabolites and gastric cancer by mediated Mendelian randomization (MR) analysis in East Asian population.

Methods

At first, summary statistics of 500 gut microbiomes, 112 blood metabolites, 7 921 gastric cancer patients, and 159 201 controls were obtained from the publicly available genome-wide association studies (GWAS) database for two-sample MR analysis.In addition, a two-step approach was used to quantify the proportion of blood metabolite-mediated effects of gut microbiome on gastric cancer.The inverse variance weighted (IVW)method was the primary effect estimation method, while the MR-Egger, weighted median, simple mode,and weighted mode were used as supplements to the IVW method, and sensitivity analyses were utilized to validate the reliability of the MR results.

Results

14 gut microbes were significantly associated with gastric cancer in East Asians, of which 8 were identified as risk factors.Two-step MR analysis identified three metabolic functional pathways (rhamnose degradation, arginine degradation I, and pentose phosphate pathway of non-oxidative branch) that were causally associated with gastric cancer in East Asians through the mediation of two blood metabolites (hydrocortisone and vitamin K), with vitamin K showing the highest mediation proportion (13.5% and 16.2%).

Conclusion

Blood metabolites represented by hydrocortisone and vitamin K, may mediate the pathogenic process of gastric cancer by gut microbiota, providing new ideas for the diagnosis, treatment, and early prevention of gastric cancer.

表1 肠道微生物组与胃癌之间的双向双样本孟德尔随机化分析结果
表2 中介孟德尔随机化分析的中介效应值和占比
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