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Relationship between gut microbiota and pancreatic cancer in East Asians: genetic evidence based on Mendelian randomization
- DU Kaihao, HOU Lizhao, DONG Xiaoge, XUE Weiwei, HE Jiejie, LUO Lanminghui, JIANG Wei, WANG Zhanjin, WANG Zhan
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Journal of Shandong University (Health Sciences). 2025, 63(12):
44-52.
doi:10.6040/j.issn.1671-7554.0.2024.1248
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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.