基于肠道菌群和代谢组学构建溃疡性结肠炎伴艰难梭菌感染的诊断模型

Construction of a diagnostic model for ulcerative colitis with Clostridioides difficile infection based on intestinal flora and metabolomics

目的基于临床资料、微生物及微生物代谢物,构建溃疡性结肠炎(UC)患者存在艰难梭菌(CD)感染的诊断模型。方法将2018—2019年就诊于空军军医大学西京医院的58名UC患者纳入本研究,分为UC未合并CD感染组(n=29)和UC合并CD感染组(n=29)。比较两组的临床资料、菌群和代谢物差异,并应用logistic回归分析建立UC患者存在CD感染的诊断模型,通过受试者工作特征曲线下面积(AUC)和拟合优度检验评估诊断模型效能。结果单因素分析结果显示粪便微生物代谢物十六烷、乳酸、松柏醇、3苯基乳酸、C反应蛋白、ClostridiumⅪ与UC患者CD感染有关(P<0.05),多因素分析结果显示十六烷、乳酸、ClostridiumⅪ是UC患者是否存在CD感染的独立预测因子。通过3因子建立logistic回归模型:logit(P)=0.724-0.980×十六烷+1.512×乳酸+1.298×ClostridiumⅪ。该模型的AUC为0.873(95%CI:0.782~0.964),约登指数最大(0.655)时该模型的诊断阈值0.411,敏感度79.3%,特异度86.2%。Hosmer-Lemeshow检验χ^(2)=5.381,P=0.716。结论基于肠道微生物及其微生物代谢物建立的UC患者发生CD感染的临床诊断模型,具有良好的效能,可为进一步临床决策提供参考。

Objective To establish a diagnostic model for the presence of Clostridioides difficile(CD)infection in patients with ulcerative colitis(UC)based on clinical data,microorganisms and microbial metabolites.Methods Fifty-eight UC patients in Xijing Hospital,Air Force Medical University from 2018 to 2019 were included in this study and divided into UC group without CD infection(n=29)and UC group with CD infection(n=29).The differences in clinical data,flora and metabolites between the two groups were compared,and logistic regression analysis was used to establish a diagnostic model for the presence of CD infection in UC patients.The efficacy of the diagnostic model was evaluated by area under the receiver operating characteristic curve(AUC)and goodness-of-fit test.Results The results of univariate analysis showed that the fecal microbial metabolites hexadecane,lactic acid,coniferyl alcohol,3-phenyllactic acid,C-reactive protein,and ClostridiumⅪwere associated with CD infection in UC patients(P<0.05),and the results of multivariate analysis showed that hexadecane,lactic acid,and ClostridiumⅪwere independent predictors of the presence of CD infection in UC patients.A logistic regression model was established with 3 factors:logit(P)=0.724-0.980×hexadecane+1.512×lactic acid+1.298×ClostridiumⅪ.The AUC of this model was 0.873(95%CI:0.782-0.964),and the diagnostic threshold of this model was 0.411 at the maximum of the Youden s index(0.655),with a sensitivity of 79.3%and a specificity of 86.2%.In Hosmer-Lemeshow test,χ^(2)=5.381 and P was 0.716.Conclusion The clinical diagnostic model of CD infection in UC patients based on intestinal microorganisms and microbial metabolites has good efficacy and can provide reference for further clinical decision-making.