Metabolomics reveals key biomarkers for ischemic stroke: a systematic review of emerging evidence

ObjectiveTo systematically collate and evaluate metabolomics-based biomarkers of ischemic stroke (IS) to guide clinical diagnosis and treatment.MethodsComprehensive literature searches were conducted in PubMed, Embase, and Web of Science using “IS” and “metabolomics” as core keywords, covering publi...

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Main Authors: Lu Ding, Meiling Zhang, Baochao Fan, Fuyuan Deng, Zhenyuan Li, Yixuan Han, Yifan Wu, Jingchun Zeng, Liming Lu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Neurology
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Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2025.1630390/full
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author Lu Ding
Lu Ding
Meiling Zhang
Baochao Fan
Fuyuan Deng
Zhenyuan Li
Yixuan Han
Yifan Wu
Jingchun Zeng
Jingchun Zeng
Liming Lu
author_facet Lu Ding
Lu Ding
Meiling Zhang
Baochao Fan
Fuyuan Deng
Zhenyuan Li
Yixuan Han
Yifan Wu
Jingchun Zeng
Jingchun Zeng
Liming Lu
author_sort Lu Ding
collection DOAJ
description ObjectiveTo systematically collate and evaluate metabolomics-based biomarkers of ischemic stroke (IS) to guide clinical diagnosis and treatment.MethodsComprehensive literature searches were conducted in PubMed, Embase, and Web of Science using “IS” and “metabolomics” as core keywords, covering publications up through February 2024. Any original metabolomic research related to IS was selected. Key information such as study demographics, study type, objectives, metabolomic analysis methods, and main findings were extracted and analyzed. Frequently mentioned metabolites were subjected to enrichment analysis using the MetaboAnalyst 6.0 platform.ResultsA total of 51 studies were included. Quality assessment revealed that 54.8% of the diagnostic studies and 69.2% of the prognostic studies were high-quality, with most controlling for confounding factors. Metabolite analysis revealed associations between decreased proline, isoleucine, valine, and alanine levels with IS. Increased tyrosine, glutamine, phenylalanine, sphingomyelin, glutamate, lactate and glucose, and decreased LysoPC (18:2), histidine, and methionine levels were linked to IS onset. Specific metabolite combinations, such as serine, isoleucine, betaine, PC (5:0/5:0), and LysoPE (18:2), showed high precision in predicting acute ischemic stroke (AIS) (training set AUC = 0.988, test set AUC = 0.971). Glycine-serine-threonine and valine-leucine-isoleucine pathways were significant in diagnosing IS and AIS, and in differentiating ischemic and hemorrhagic strokes, as well as identifying post-stroke depression and cognitive impairment.ConclusionThis study confirms the potential diagnostic and prognostic value of changes in amino acids and lipids, as well as other metabolites and metabolic pathways, in IS. These findings highlight the promise of metabolomics in IS diagnosis, differential diagnosis, risk assessment, and complication identification. However, further validation is needed due to the varying quality of the included studies.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier CRD42022335505.
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spelling doaj-art-3248a6a69ef5435fb6c7cdb75b68d4bb2025-08-20T03:41:08ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-08-011610.3389/fneur.2025.16303901630390Metabolomics reveals key biomarkers for ischemic stroke: a systematic review of emerging evidenceLu Ding0Lu Ding1Meiling Zhang2Baochao Fan3Fuyuan Deng4Zhenyuan Li5Yixuan Han6Yifan Wu7Jingchun Zeng8Jingchun Zeng9Liming Lu10Department of Traditional Chinese Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaClinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, ChinaClinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, ChinaClinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, ChinaClinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, ChinaMedical Department, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, ChinaSchool of European Languages and Cultures, Beijing Foreign Studies University, Beijing, ChinaCollege of Physical Education and Public Health, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Rehabilitation, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, ChinaShenShan Hospital, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Shanwei, ChinaClinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, ChinaObjectiveTo systematically collate and evaluate metabolomics-based biomarkers of ischemic stroke (IS) to guide clinical diagnosis and treatment.MethodsComprehensive literature searches were conducted in PubMed, Embase, and Web of Science using “IS” and “metabolomics” as core keywords, covering publications up through February 2024. Any original metabolomic research related to IS was selected. Key information such as study demographics, study type, objectives, metabolomic analysis methods, and main findings were extracted and analyzed. Frequently mentioned metabolites were subjected to enrichment analysis using the MetaboAnalyst 6.0 platform.ResultsA total of 51 studies were included. Quality assessment revealed that 54.8% of the diagnostic studies and 69.2% of the prognostic studies were high-quality, with most controlling for confounding factors. Metabolite analysis revealed associations between decreased proline, isoleucine, valine, and alanine levels with IS. Increased tyrosine, glutamine, phenylalanine, sphingomyelin, glutamate, lactate and glucose, and decreased LysoPC (18:2), histidine, and methionine levels were linked to IS onset. Specific metabolite combinations, such as serine, isoleucine, betaine, PC (5:0/5:0), and LysoPE (18:2), showed high precision in predicting acute ischemic stroke (AIS) (training set AUC = 0.988, test set AUC = 0.971). Glycine-serine-threonine and valine-leucine-isoleucine pathways were significant in diagnosing IS and AIS, and in differentiating ischemic and hemorrhagic strokes, as well as identifying post-stroke depression and cognitive impairment.ConclusionThis study confirms the potential diagnostic and prognostic value of changes in amino acids and lipids, as well as other metabolites and metabolic pathways, in IS. These findings highlight the promise of metabolomics in IS diagnosis, differential diagnosis, risk assessment, and complication identification. However, further validation is needed due to the varying quality of the included studies.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier CRD42022335505.https://www.frontiersin.org/articles/10.3389/fneur.2025.1630390/fullischemic strokemetabolomicsbiomarkersdiagnosisrisk predictionprognosis
spellingShingle Lu Ding
Lu Ding
Meiling Zhang
Baochao Fan
Fuyuan Deng
Zhenyuan Li
Yixuan Han
Yifan Wu
Jingchun Zeng
Jingchun Zeng
Liming Lu
Metabolomics reveals key biomarkers for ischemic stroke: a systematic review of emerging evidence
Frontiers in Neurology
ischemic stroke
metabolomics
biomarkers
diagnosis
risk prediction
prognosis
title Metabolomics reveals key biomarkers for ischemic stroke: a systematic review of emerging evidence
title_full Metabolomics reveals key biomarkers for ischemic stroke: a systematic review of emerging evidence
title_fullStr Metabolomics reveals key biomarkers for ischemic stroke: a systematic review of emerging evidence
title_full_unstemmed Metabolomics reveals key biomarkers for ischemic stroke: a systematic review of emerging evidence
title_short Metabolomics reveals key biomarkers for ischemic stroke: a systematic review of emerging evidence
title_sort metabolomics reveals key biomarkers for ischemic stroke a systematic review of emerging evidence
topic ischemic stroke
metabolomics
biomarkers
diagnosis
risk prediction
prognosis
url https://www.frontiersin.org/articles/10.3389/fneur.2025.1630390/full
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