Urine Metabolites as Biomarkers and Metabolism Mechanism Studies of Alcohol-Associated Liver Disease
Background/Aims: We explored the possibility of using urine polar metabolites as non-invasive biomarkers of alcohol-associated liver disease (ALD) for early-stage diagnosis and severity assessment, as well as the possible changes in metabolic pathways in ALD patients. Methods: Polar metabolites were...
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2025-06-01
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| Series: | International Journal of Translational Medicine |
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| Online Access: | https://www.mdpi.com/2673-8937/5/2/21 |
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| author | Liqing He Vatsalya Vatsalya Raobo Xu Xinmin Yin Xipeng Ma Seongho Kim Eugene G. Mueller Wenke Feng Craig J. McClain Xiang Zhang |
| author_facet | Liqing He Vatsalya Vatsalya Raobo Xu Xinmin Yin Xipeng Ma Seongho Kim Eugene G. Mueller Wenke Feng Craig J. McClain Xiang Zhang |
| author_sort | Liqing He |
| collection | DOAJ |
| description | Background/Aims: We explored the possibility of using urine polar metabolites as non-invasive biomarkers of alcohol-associated liver disease (ALD) for early-stage diagnosis and severity assessment, as well as the possible changes in metabolic pathways in ALD patients. Methods: Polar metabolites were extracted with 80% methanol, and parallel 2DLC-MS was used for polar metabolite quantification. Results: Data from untargeted metabolomics showed that 194 metabolites were significantly changed in patients, and three metabolites can differentiate healthy controls (HC), non-severe ALD, and severe alcohol-associated hepatitis (severe AH) with high accuracy (0.92–0.97). Pathway analysis showed that arginine biosynthesis and histidine metabolism pathways were among the pathways containing the metabolites that were most altered in the urine of patients. Metabolites in the urea cycle, histidine catabolism, and histidine dipeptides pathways were notably increased in the urine of ALD patients, but none of the metabolites in these two pathways can simultaneously differentiate patients from healthy volunteers and non-severe ALD from severe AH. As the top differentiated pathways, the alterations of arginine biosynthesis and histidine metabolism indicate their importance in the metabolic dysfunction of ALD. Conclusions: Our results show that the abundance changes of specific metabolites can differentiate the disease severity of ALD, showing the potential of urine polar metabolites as non-invasive biomarkers for early-stage diagnosis and disease severity assessment of ALD. |
| format | Article |
| id | doaj-art-ebbe485dfdb846588daba0cc11119108 |
| institution | Kabale University |
| issn | 2673-8937 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Translational Medicine |
| spelling | doaj-art-ebbe485dfdb846588daba0cc111191082025-08-20T03:24:39ZengMDPI AGInternational Journal of Translational Medicine2673-89372025-06-01522110.3390/ijtm5020021Urine Metabolites as Biomarkers and Metabolism Mechanism Studies of Alcohol-Associated Liver DiseaseLiqing He0Vatsalya Vatsalya1Raobo Xu2Xinmin Yin3Xipeng Ma4Seongho Kim5Eugene G. Mueller6Wenke Feng7Craig J. McClain8Xiang Zhang9Department of Chemistry, University of Louisville, Louisville, KY 40292, USAAlcohol Research Center, University of Louisville, Louisville, KY 40202, USADepartment of Chemistry, University of Louisville, Louisville, KY 40292, USADepartment of Chemistry, University of Louisville, Louisville, KY 40292, USADepartment of Chemistry, University of Louisville, Louisville, KY 40292, USADepartment of Oncology, Wayne State University, Detroit, MI 48201, USADepartment of Chemistry, University of Louisville, Louisville, KY 40292, USAAlcohol Research Center, University of Louisville, Louisville, KY 40202, USAAlcohol Research Center, University of Louisville, Louisville, KY 40202, USADepartment of Chemistry, University of Louisville, Louisville, KY 40292, USABackground/Aims: We explored the possibility of using urine polar metabolites as non-invasive biomarkers of alcohol-associated liver disease (ALD) for early-stage diagnosis and severity assessment, as well as the possible changes in metabolic pathways in ALD patients. Methods: Polar metabolites were extracted with 80% methanol, and parallel 2DLC-MS was used for polar metabolite quantification. Results: Data from untargeted metabolomics showed that 194 metabolites were significantly changed in patients, and three metabolites can differentiate healthy controls (HC), non-severe ALD, and severe alcohol-associated hepatitis (severe AH) with high accuracy (0.92–0.97). Pathway analysis showed that arginine biosynthesis and histidine metabolism pathways were among the pathways containing the metabolites that were most altered in the urine of patients. Metabolites in the urea cycle, histidine catabolism, and histidine dipeptides pathways were notably increased in the urine of ALD patients, but none of the metabolites in these two pathways can simultaneously differentiate patients from healthy volunteers and non-severe ALD from severe AH. As the top differentiated pathways, the alterations of arginine biosynthesis and histidine metabolism indicate their importance in the metabolic dysfunction of ALD. Conclusions: Our results show that the abundance changes of specific metabolites can differentiate the disease severity of ALD, showing the potential of urine polar metabolites as non-invasive biomarkers for early-stage diagnosis and disease severity assessment of ALD.https://www.mdpi.com/2673-8937/5/2/21histidine metabolismarginine biosynthesis pathwaydiagnostic biomarkeralcohol-associated liver diseasemetabolomics |
| spellingShingle | Liqing He Vatsalya Vatsalya Raobo Xu Xinmin Yin Xipeng Ma Seongho Kim Eugene G. Mueller Wenke Feng Craig J. McClain Xiang Zhang Urine Metabolites as Biomarkers and Metabolism Mechanism Studies of Alcohol-Associated Liver Disease International Journal of Translational Medicine histidine metabolism arginine biosynthesis pathway diagnostic biomarker alcohol-associated liver disease metabolomics |
| title | Urine Metabolites as Biomarkers and Metabolism Mechanism Studies of Alcohol-Associated Liver Disease |
| title_full | Urine Metabolites as Biomarkers and Metabolism Mechanism Studies of Alcohol-Associated Liver Disease |
| title_fullStr | Urine Metabolites as Biomarkers and Metabolism Mechanism Studies of Alcohol-Associated Liver Disease |
| title_full_unstemmed | Urine Metabolites as Biomarkers and Metabolism Mechanism Studies of Alcohol-Associated Liver Disease |
| title_short | Urine Metabolites as Biomarkers and Metabolism Mechanism Studies of Alcohol-Associated Liver Disease |
| title_sort | urine metabolites as biomarkers and metabolism mechanism studies of alcohol associated liver disease |
| topic | histidine metabolism arginine biosynthesis pathway diagnostic biomarker alcohol-associated liver disease metabolomics |
| url | https://www.mdpi.com/2673-8937/5/2/21 |
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