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已发表论文
血浆胆汁酸谱分析揭示了儿童脓毒症的新型早期诊断生物标志物
Authors Zhang L, Liu J , Chen Y, Lu X, Li K, Li W, Li N, Li F, Wang Y, He D , Sun Z, Guo L, Zhang Q
Received 21 May 2025
Accepted for publication 16 December 2025
Published 26 December 2025 Volume 2025:18 Pages 18151—18163
DOI https://doi.org/10.2147/JIR.S541871
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Anh Ngo
Lipeng Zhang,1– 3,* Jing Liu,1,* Yuanmei Chen,1 Xiuxiu Lu,4 Ke Li,5 Wei Li,4 Ning Li,4 Fan Li,6 Yuanyuan Wang,7 Danni He,8 Zhongyuan Sun,4 Linying Guo,9 Qi Zhang1,2
1Department of Pediatrics, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Pediatrics, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Intensive Care Unit, Capital Center for Children’s Health, Capital medical university, Beijing, People’s Republic of China; 5China National Clinical Research Center of Neurological Diseases, Advanced Innovation Center for Human Brain Protection, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Department of Neonatology, Guangzhou Women and Children’s Medical Center, Guangzhou, People’s Republic of China; 7Department of Respiratory Intervention, Qilu Children’s Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 8Department of Urology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 9Department of Emergency, Capital center for Children’s Health, Capital medical University, Beijing, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Qi Zhang, Email zhangqikeyan@163.com
Purpose: Sepsis is a life-threatening condition, and early detection remains a challenge. While bile acids have been implicated in various diseases, their role as biomarkers for sepsis is underexplored. This study aims to identify metabolites associated with sepsis and assess the potential of bile acids for early diagnosis and prognosis of pediatric sepsis.
Methods: We enrolled 100 participants in the discovery phase and 141 participants in the validation phase. Non-targeted liquid chromatography-mass spectrometry (LC-MS) metabolomics analyses were performed to identify differential metabolites between sepsis patients and healthy controls. Targeted quantitative analysis of 12 plasma bile acids (BA) was conducted to assess their concentrations. Machine learning algorithms, including Recursive Feature Elimination (RFE), Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), Support Vector Machine-RFE (SVM-RFE), and Gradient Boosting Decision Tree (GBDT), were employed to identify key BAs for sepsis diagnosis.
Results: Untargeted metabolomics revealed bile acid pathway dysregulation, validated by targeted quantification showing elevated primary bile acids—cholic acid (CA), glycocholic acid (GCA), taurocholic acid (TCA), glycochenodeoxycholic acid (GCDCA), taurochenodeoxycholic acid (TCDCA)—and taurine-conjugated secondary bile acid TDCA (p< 0.05). Conversely, secondary bile acids deoxycholic acid (DCA), glycodeoxycholic acid (GDCA), ursodeoxycholic acid (UDCA), glycoursodeoxycholic acid (GUDCA), and lithocholic acid (LCA) were significantly reduced (p< 0.05). Univariate logistic regression identified TCA, TDCA, GCA, TCDCA, GCDCA, and TDCA/DCA as risk factors for sepsis, while LCA, DCA, UDCA, GUDCA, and DCA/CA were protective factors. Five machine learning models identified four bile acid indicators—UDCA, GUDCA, GCA, DCA—as key predictors for sepsis diagnosis, with a combined model area under the curve (AUC) of 0.880. Additionally, DCA/CA and GCDCA were important predictors for septic shock, with risks increasing by 4.5% (OR = 1.045, 95% CI: 1.009– 1.081) and 30% (OR = 0.700, 95% CI: 0.526– 0.932), respectively. LCA was a risk factor for respiratory failure in sepsis, with an OR of 2.154 (95% CI: 1.022– 4.540).
Conclusion: Our results highlight the potential of bile acid profiling as a diagnostic and prognostic biomarker for pediatric sepsis. These findings suggest a path toward early intervention, improving patient outcomes by enabling timely detection and treatment.
Keywords: sepsis, bile acids, metabolomics, biomarkers, liquid chromatography-mass spectrometry, LC-MS, pediatric
1Department of Pediatrics, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Pediatrics, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Intensive Care Unit, Capital Center for Children’s Health, Capital medical university, Beijing, People’s Republic of China; 5China National Clinical Research Center of Neurological Diseases, Advanced Innovation Center for Human Brain Protection, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Department of Neonatology, Guangzhou Women and Children’s Medical Center, Guangzhou, People’s Republic of China; 7Department of Respiratory Intervention, Qilu Children’s Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 8Department of Urology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 9Department of Emergency, Capital center for Children’s Health, Capital medical University, Beijing, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Qi Zhang, Email zhangqikeyan@163.com
Purpose: Sepsis is a life-threatening condition, and early detection remains a challenge. While bile acids have been implicated in various diseases, their role as biomarkers for sepsis is underexplored. This study aims to identify metabolites associated with sepsis and assess the potential of bile acids for early diagnosis and prognosis of pediatric sepsis.
Methods: We enrolled 100 participants in the discovery phase and 141 participants in the validation phase. Non-targeted liquid chromatography-mass spectrometry (LC-MS) metabolomics analyses were performed to identify differential metabolites between sepsis patients and healthy controls. Targeted quantitative analysis of 12 plasma bile acids (BA) was conducted to assess their concentrations. Machine learning algorithms, including Recursive Feature Elimination (RFE), Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), Support Vector Machine-RFE (SVM-RFE), and Gradient Boosting Decision Tree (GBDT), were employed to identify key BAs for sepsis diagnosis.
Results: Untargeted metabolomics revealed bile acid pathway dysregulation, validated by targeted quantification showing elevated primary bile acids—cholic acid (CA), glycocholic acid (GCA), taurocholic acid (TCA), glycochenodeoxycholic acid (GCDCA), taurochenodeoxycholic acid (TCDCA)—and taurine-conjugated secondary bile acid TDCA (p< 0.05). Conversely, secondary bile acids deoxycholic acid (DCA), glycodeoxycholic acid (GDCA), ursodeoxycholic acid (UDCA), glycoursodeoxycholic acid (GUDCA), and lithocholic acid (LCA) were significantly reduced (p< 0.05). Univariate logistic regression identified TCA, TDCA, GCA, TCDCA, GCDCA, and TDCA/DCA as risk factors for sepsis, while LCA, DCA, UDCA, GUDCA, and DCA/CA were protective factors. Five machine learning models identified four bile acid indicators—UDCA, GUDCA, GCA, DCA—as key predictors for sepsis diagnosis, with a combined model area under the curve (AUC) of 0.880. Additionally, DCA/CA and GCDCA were important predictors for septic shock, with risks increasing by 4.5% (OR = 1.045, 95% CI: 1.009– 1.081) and 30% (OR = 0.700, 95% CI: 0.526– 0.932), respectively. LCA was a risk factor for respiratory failure in sepsis, with an OR of 2.154 (95% CI: 1.022– 4.540).
Conclusion: Our results highlight the potential of bile acid profiling as a diagnostic and prognostic biomarker for pediatric sepsis. These findings suggest a path toward early intervention, improving patient outcomes by enabling timely detection and treatment.
Keywords: sepsis, bile acids, metabolomics, biomarkers, liquid chromatography-mass spectrometry, LC-MS, pediatric