肝胆胰外科杂志2026，Vol.38Issue(6)：408-418,11.DOI:10.11952/j.issn.1007-1954.2026.06.005
胆汁菌群及胆汁酸谱与胆囊结石的相关性分析
Correlation of bile microbiota and bile acid profiles with cholecystolithiasis
摘要
Abstract
Objective To investigate the correlation between cholecystolithiasis and bile microbiota as well as bile acid profiles,and to construct a predictive model for cholecystolithiasis.Methods A retrospective study was conducted involving 35 patients who underwent surgical resection at the Second Affiliated Hospital of Harbin Medical University and The Affiliated Cancer Hospital of Harbin Medical University from September 2024 to May 2025.Patients diagnosed with cholecystolithiasis who underwent laparoscopic cholecystectomy were assigned to the cholecystolithiasis group(Group S,n=25),and patients diagnosed with primary liver cancer who underwent radical resection with no cholecystolithiasis were assigned to the non-cholecystolithiasis group(Group N,n=10).Clinical data were compared between the two groups.Bile samples were collected from both groups for 16S rDNA sequencing and targeted metabolomics analysis.Alpha and beta diversity analyses were performed on the bile microbiota sequencing results to assess differences in microbial diversity,and changes in microbial composition along with representative differential taxa were analyzed.Differential metabolites exhibiting the greatest increase or decrease in bile samples from Group S were screened.Receiver operating characteristic(ROC)curves were generated and the area under the curve(AUC)was calculated.Differential bile metabolites with an AUC≥0.7 were selected to establish a combined predictive model.A microbe-metabolite network was constructed,and Spearman's rank correlation test was used to analyze the correlation between differential bile metabolites and microbial communities.Results No statistically significant differences were observed in baseline clinical characteristics between the two groups(all P>0.05).Analysis of bile microbiota diversity revealed that both alpha diversity and beta diversity were significantly reduced in Group S(P<0.05).Species composition and differential species analysis indicated that cholecystolithiasis was significantly associated with alterations in bile microbiota composition.Differential analysis of bile metabolites showed significant changes in multiple bile acid levels in Group S,primarily characterized by elevated levels of secondary bile acids and their conjugates.Five bile acids including ursodeoxycholic acid-3-sulfate,taurocholic acid-3-sulfate,lithocholic acid,glycocholic acid-3-sulfate,and chenodeoxycholic acid-24-acyl-β-D-glucuronide exhibited an AUC≥0.7 in ROC analysis for predicting cholecystolithiasis.The combined predictive model established based on these metabolites achieved an AUC of 0.926.Microbe-metabolite network correlation analysis revealed that Rubellimicrobium was significantly positively correlated with elevated bile acid levels in Group S(all P<0.05).Conclusion Cholecystolithiasis is correlated with alterations in bile microbiota and bile acid profiles.The combined predictive model constructed based on differential bile acids demonstrates satisfactory diagnostic performance.关键词
胆囊结石/胆汁菌群/胆汁酸/16S rDNA测序/靶向代谢组学/多组学分析Key words
cholecystolithiasis/bile microbiota/bile acids/16S rDNA sequencing/targeted metabolomics/multi-omics分类
医药卫生引用本文复制引用
荆小伟,吴德海,邰升..胆汁菌群及胆汁酸谱与胆囊结石的相关性分析[J].肝胆胰外科杂志,2026,38(6):408-418,11.基金项目
国家自然科学基金面上项目(82373111). （82373111）
