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山东大学学报 (医学版) ›› 2025, Vol. 63 ›› Issue (12): 44-52.doi: 10.6040/j.issn.1671-7554.0.2024.1248

• 临床医学 • 上一篇    

东亚人肠道菌群与胰腺癌关系:基于孟德尔随机化方法的遗传学证据

杜凯豪1,侯立朝2,东小鸽1,薛伟伟1,何洁洁1,罗兰明慧1,蒋威1,汪占金1,王展2,3   

  1. 1.青海大学临床医学院, 青海 西宁 810016;2.青海大学附属医院肝胆胰外科, 青海 西宁 810001;3.青海大学附属医院医工结合与转化应用部, 青海 西宁 810001
  • 发布日期:2025-12-19
  • 通讯作者: 王展. E-mail:ufofu01@163.com
  • 基金资助:
    国家自然科学基金(82160131)

Relationship between gut microbiota and pancreatic cancer in East Asians: genetic evidence based on Mendelian randomization

DU Kaihao1, HOU Lizhao2, DONG Xiaoge1, XUE Weiwei1, HE Jiejie1, LUO Lanminghui1, JIANG Wei1, WANG Zhanjin1, WANG Zhan2,3   

  1. 1. Qinghai University Clinical Medical College, Xining 810016, Qinghai, China;;
    2. Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai, China;;
    3. Department of Medical Engineering Integration and Translational Application, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai, China)
  • Published:2025-12-19

PDF (PC)

3

摘要： 目的 探讨东亚人群中肠道菌群(gut microbiota, GM)与胰腺癌(pancreatic cancer, PC)之间的因果关系,揭示PC的潜在病理机制,为临床干预提供理论依据。 方法 采用孟德尔随机化(Mendelian randomization, MR)分析方法,利用全基因组关联研究(genome-wide association studies, GWAS)数据库中的数据,以单核苷酸多态性作为工具变量,通过逆方差加权、加权中位数法、贝叶斯加权MR等多种MR方法评估析500种东亚人群GM与PC之间的因果关系。 结果 逆方差加权法结果显示,厄雷莫球菌属［日本生物银行(Biobank Japan, BBJ):OR=0.847,95%CI:0.734~0.978,P=0.024;欧洲生物信息研究所(European Bioinformatics Institute, EBI):OR=0.829,95%CI:0.727~0.945,P=0.005)］、鲍曼不动杆菌种(BBJ:OR=0.775,95%CI:0.667~0.900,P=0.001;EBI:OR=0.828,95%CI:0.731~0.937,P=0.003)、甲硫氨酸代谢途径I(MF0038)(BBJ:OR=0.299,95%CI:0.097~0.917,P=0.035;EBI:OR=0.260,95%CI:0.110~0.615,P=0.002)、螺杆菌属(BBJ:OR=0.771,95%CI:0.657~0.905,P=0.001;EBI:OR=0.807,95%CI:0.700~0.930,P=0.003)与PC的发生风险降低相关;阿姆尼普雷沃菌种(BBJ:OR=1.328,95%CI:1.086~1.623,P=0.006;EBI:OR=1.258,95%CI:1.041~1.520,P=0.018)、沙利特罗拟杆菌种(BBJ:OR=1.473,95%CI:1.150~1.887,P=0.002;EBI:OR=1.242,95%CI:1.030~1.497,P=0.023)、食酸菌属(BBJ:OR=1.184,95%CI:1.021~1.374,P=0.026;EBI:OR=1.166,95%CI:1.015~1.339,P=0.030)与PC的发生风险增加相关。贝叶斯加权MR结果显示,厄雷莫球菌属(BBJ:OR=0.844,95%CI:0.725~0.983,P=0.029;EBI:OR=0.825,95%CI:0.717~0.949,P=0.007)、鲍曼不动杆菌种(BBJ:OR=0.766,95%CI:0.647~0.906,P=0.002;EBI:OR=0.823,95%CI:0.720~0.939,P=0.004)、甲硫氨酸代谢途径I(MF0038)(BBJ:OR=0.270,95%CI:0.082~0.0888,P=0.031;EBI:OR=0.245,95%CI:0.098~0.610,P=0.003)、螺杆菌属(BBJ:OR=0.768,95%CI:0.647~0.912,P=0.003;EBI:OR=0.802,95%CI:0.689~0.934,P=0.004)与PC的发生风险降低相关;阿姆尼普雷沃菌种(BBJ:OR=1.340,95%CI:1.076~1.668,P=0.009;EBI:OR=1.262,95%CI:1.030~1.547,P=0.025)、沙利特罗拟杆菌种(BBJ:OR=1.487,95%CI:1.145~1.931,P=0.003;EBI:OR=1.256,95%CI:1.031~1.531,P=0.024)、食酸菌属(BBJ:OR=1.189,95%CI:1.017~1.390,P=0.029;EBI:OR=1.170,95%CI:1.011~1.353,P=0.036)与PC的发生风险增加相关。敏感性分析提示研究结果稳健。 结论 厄雷莫球菌属、鲍曼不动杆菌种、甲硫氨酸代谢途径I(MF0038)和螺杆菌属是PC的保护因素,而阿姆尼普雷沃菌种、沙利特罗拟杆菌种、食酸菌属会增加PC的发生风险。

关键词: 肠道菌群, 胰腺癌, 孟德尔随机化, 全基因组关联研究, 单核苷酸多态性

Abstract: Objective To explore the causal relationship between gut microbiota(GM)and pancreatic cancer(PC)in East Asians to reveal the potential pathological mechanisms of PC and provide a theoretical basis for clinical interventions. Methods Mendelian randomization(MR)analysis was conducted using data from genome-wide association studies(GWAS)databases to analyze the relationships between 500 gut microbiota features and PC in East Asians. Single nucleotide polymorphisms were used as instrumental variables, and various MR methods, including inverse variance weighting(IVW), weighted median method, and Bayesian weighted MR, were employed to assess the causal relationship between GM and PC. Results The results of the inverse-variance weighted method showed that g_Eremococcus ［Biobank Japan(BBJ): OR=0.847, 95%CI: 0.734-0.978, P=0.024; European Bioinformatics Institute(EBI): OR=0.829, 95%CI: 0.727-0.945, P=0.005), s_Acinetobacter_baumannii(BBJ: OR=0.775, 95%CI: 0.667-0.900, P=0.001; EBI: OR=0.828, 95%CI: 0.731-0.937, P=0.003), methionine metabolism I(MF0038)(BBJ: OR=0.299, 95%CI: 0.097-0.917, P=0.035; EBI: OR=0.260, 95%CI: 0.110-0.615, P=0.002), and g_Helicobacter(BBJ: OR=0.771, 95%CI: 0.657-0.905, P=0.001; EBI: OR=0.807, 95%CI: 0.700-0.930, P=0.003)were associated with a reduced risk of PC, whereas s_Prevotella_amnii(BBJ: OR=1.328, 95%CI: 1.086-1.623, P=0.006; EBI: OR=1.258, 95%CI: 1.041-1.520, P=0.018), s_Bacteroides_salanitronis(BBJ: OR=1.473, 95%CI: 1.150-1.887, P=0.002; EBI: OR=1.242, 95%CI: 1.030-1.497, P=0.023), and g_Acidovorax(BBJ: OR=1.184, 95%CI: 1.021-1.374, P=0.026; EBI: OR=1.166, 95%CI: 1.015-1.339, P=0.030)were associated with an increased risk of PC, and the results of the Bayesian weighted MR method similarly showed that g_Eremococcus(BBJ: OR=0.844, 95%CI: 0.725-0.983, P=0.029; EBI: OR=0.825, 95%CI: 0.717-0.949, P=0.007), s_Acinetobacter_baumannii(BBJ: OR=0.766, 95%CI: 0.647-0.906, P=0.002; EBI: OR=0.823, 95%CI: 0.720-0.939, P=0.004), methionine metabolism I(MF0038)(BBJ: OR=0.270, 95%CI: 0.082-0.888, P=0.031; EBI: OR=0.245, 95%CI: 0.098-0.610, P=0.003), and g_Helicobacter(BBJ: OR=0.768, 95%CI: 0.647-0.912, P=0.003; EBI: OR=0.802, 95%CI: 0.689-0.934, P=0.004)were associated with a reduced risk of PC, while s_Prevotella_amnii(BBJ: OR=1.340, 95%CI: 1.076-1.668, P=0.009; EBI: OR=1.262, 95%CI: 1.030-1.547, P=0.025), s_Bacteroides_salanitronis(BBJ: OR=1.487, 95%CI: 1.145-1.931, P=0.003; EBI: OR=1.256, 95%CI: 1.031-1.531, P=0.024), and g_Acidovorax(BBJ: OR=1.189, 95%CI: 1.017-1.390, P=0.029; EBI: OR=1.170, 95%CI: 1.011-1.353, P=0.036)were associated with an increased risk of PC. Sensitivity analyses suggested that the results were robust. Conclusion g_Eremococcus, s_Acinetobacter_baumannii, methionine metabolism pathway I(MF0038), and g_Helicobacter may serve as protective factors for PC, while s_Prevotella_amnii, s_Bacteroides_salanitronis, and g_Acidovorax may increase the risk of PC.

Key words: Gut microbiota, Pancreatic cancer, Mendelian randomization, Genome-wide association study, Single nucleotide polymorphisms

中图分类号: 

  • R735.9
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