肠道菌群与急慢性胰腺炎的因果关系:一项双样本孟德尔随机化研究

Causality between gut microbiota and acute/chronic pancreatitis:A two-sample Mendelian randomization study

目的运用双样本孟德尔随机化(TSMR)评估肠道菌群与急、慢性胰腺炎(AP/CP)发生风险之间的因果关系。方法通过FinnGen consortium R10获得AP/CP的全基因组关联研究数据(GWAS),通过Lopera-Maya等的研究获得肠道菌群的GWAS。对基于GWAS的所有汇总数据进行二次数据分析,选择与肠道菌群密切关联的遗传位点作为工具变量,分别用逆方差加权法(IVW)、MR-Egger回归法、加权中位数法(WME)和加权模式法(WM)进行TSMR分析,以OR值评价肠道菌群与AP/CP发生风险的关系。敏感性分析用于检验MR分析结果的稳健性和可靠性。结果本研究分析了119种肠道菌属和AP/CP的关系,发现5种肠道菌属和AP相关,2种肠道菌属和CP相关。IVW分析显示,Holdemania属(OR=1.11,95%CI1.02-1.21,P=0.019),Ruminococcus属(OR=1.16,95%CI 1.02-1.32,P=0.020)和Barnesiella属(OR=1.12,95%CI 1.00-1.24,P=0.046)与AP风险增加有关;Bacteroides属(OR=0.89,95%CI 0.79-1.00,P=0.044)和Blautia属(OR=0.82,95%CI 0.72-0.93,P=0.002)与AP风险降低有关。Parabacteroides属(OR=1.10,95%CI 1.00-1.22,P=0.038)与CP风险增加有关;Dorea属(OR=0.79,95%CI 0.63-0.99,P=0.045)与CP风险降低有关。结论本项TSMR分析表明,肠道菌群与AP/CP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AP/CP的预防和治疗。

Objective To evaluate the association between gut microbiota and the risk of acute/chronic pancreatitis(AP/CP)using two-sample Mendelian randomization(TSMR)analysis.Methods The genome-wide association study(GWAS)data for AP/CP was obtained from the FinnGen consortium R10,and the GWAS data for gut microbiota was obtained from the research of Lopera-Maya,et al.Secondary data analysis was performed on all aggregated data based on GWASs,and the genetic loci closely associated with gut microbiota were selected as instrumental variables.The inverse variance weighted(IVW),MR-Egger regression,weighted median(WME)and weighted mode(WM)methods for TSMR analysis were employed in this study.Sensitivity analysis was used to test the robustness and reliability of MR results.The odds ratio(OR)was used to evaluate the relationship between gut microbiota and the risk of AP/CP.Results The correlation between 119 gut microbiota and AP/CP was analyzed in this study.The results showed that 5 genera were associated with AP,while 2 genera were associated with CP.The IVW method revealed that,Holdemania(OR=1.11,95%CI 1.02-1.21,P=0.019),Ruminococcus(OR=1.16,95%CI 1.02-1.32,P=0.020)and Barnesiella(OR=1.12,95%CI 1.00-1.24,P=0.046)were associated with increased risk of AP;Bacteroides(OR=0.89,95%CI 0.79-1.00,P=0.044)and Blautia(OR=0.82,95%CI 0.72-0.93,P=0.002)were associated with reduced risk of AP.Parabacteroides(OR=1.10,95%CI 1.00-1.22,P=0.038)was associated with increased risk of CP;Dorea(OR=0.79,95%CI 0.63-0.99,P=0.045)was associated with reduced risk of CP.Conclusion The TSMR analysis shows that,there may be a causal relationship between gut microbiota and the risk of AP/CP,regulation of gut microbiota may contribute to the prevention and treatment of AP/CP.