Alterations in Urine Metabolomics Following Sport-Related Concussion: A 1H NMR-Based Analysis
Objective: Millions of sport-related concussions (SRC) occur annually in North America, and current diagnosis of concussion is based largely on clinical evaluations. The objective of this study was to determine whether urinary metabolites are significantly altered post-SRC compared to pre-injury.Set...
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2021.645829/full |
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| author | Zachary R. Wanner Cormac G. Southam Cormac G. Southam Prachi Sanghavi Naveenjyote S. Boora Eric J. Paxman Sean P. Dukelow Sean P. Dukelow Brian W. Benson Brian W. Benson Tony Montina Gerlinde A. S. Metz Chantel T. Debert Chantel T. Debert |
| author_facet | Zachary R. Wanner Cormac G. Southam Cormac G. Southam Prachi Sanghavi Naveenjyote S. Boora Eric J. Paxman Sean P. Dukelow Sean P. Dukelow Brian W. Benson Brian W. Benson Tony Montina Gerlinde A. S. Metz Chantel T. Debert Chantel T. Debert |
| author_sort | Zachary R. Wanner |
| collection | DOAJ |
| description | Objective: Millions of sport-related concussions (SRC) occur annually in North America, and current diagnosis of concussion is based largely on clinical evaluations. The objective of this study was to determine whether urinary metabolites are significantly altered post-SRC compared to pre-injury.Setting: Outpatient sports medicine clinic.Participants: Twenty-six male youth sport participants.Methods: Urine was analyzed pre-injury and after SRC by 1H NMR spectroscopy. Data were analyzed using multivariate statistics, pairwise t-test, and metabolic pathway analysis. Variable importance analysis based on random variable combination (VIAVC) was applied to the entire data set and resulted in a panel of 18 features. Partial least square discriminant analysis was performed exploring the separation between pre-injury and post-SRC groups. Pathway topography analysis was completed to identify biological pathway involvement. Spearman correlations provide support for the relationships between symptom burden and length of return to play and quantifiable metabolic changes in the human urinary metabolome.Results: Phenylalanine and 3-indoxysulfate were upregulated, while citrate, propylene glycol, 1-methylhistidine, 3-methylhistidine, anserine, and carnosine were downregulated following SRC. A receiver operator curve (ROC) tool constructed using the 18-feature classifier had an area under the curve (AUC) of 0.887. A pairwise t-test found an additional 19 altered features, 7 of which overlapped with the VIAVC analysis. Pathway topology analysis indicated that aminoacyl-tRNA biosynthesis and beta-alanine metabolism were the two pathways most significantly changed. There was a significant positive correlation between post-SRC 2-hydroxybutyrate and the length of return to play (ρ = 0.482, p = 0.02) as well as the number of symptoms and post-SRC lactose (ρ = 0.422, p = 0.036).Conclusion: We found that 1H NMR metabolomic urinary analysis can identify a set of metabolites that can correctly classify SRC with an accuracy of 81.6%, suggesting potential for a more objective method of characterizing SRC. Correlations to both the number of symptoms and length of return to play indicated that 2-hydroxybutyrate and lactose may have potential applications as biomarkers for sport-related concussion. |
| first_indexed | 2024-12-17T03:03:43Z |
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| last_indexed | 2024-12-17T03:03:43Z |
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| spelling | doaj.art-1bb2b64636374b5daa45148d3fa627732022-12-21T22:06:01ZengFrontiers Media S.A.Frontiers in Neurology1664-22952021-08-011210.3389/fneur.2021.645829645829Alterations in Urine Metabolomics Following Sport-Related Concussion: A 1H NMR-Based AnalysisZachary R. Wanner0Cormac G. Southam1Cormac G. Southam2Prachi Sanghavi3Naveenjyote S. Boora4Eric J. Paxman5Sean P. Dukelow6Sean P. Dukelow7Brian W. Benson8Brian W. Benson9Tony Montina10Gerlinde A. S. Metz11Chantel T. Debert12Chantel T. Debert13Department of Neuroscience, Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, AB, CanadaDepartment of Neuroscience, Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, AB, CanadaDepartment of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, CanadaDepartment of Neuroscience, Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, AB, CanadaDepartment of Neuroscience, Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, AB, CanadaDepartment of Neuroscience, Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, AB, CanadaDepartment of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, CanadaCumming School of Medicine, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, CanadaDepartment of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, CanadaWinsport Medicine Clinic, Calgary, AB, CanadaDepartment of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, AB, CanadaDepartment of Neuroscience, Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, AB, CanadaDepartment of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, CanadaCumming School of Medicine, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, CanadaObjective: Millions of sport-related concussions (SRC) occur annually in North America, and current diagnosis of concussion is based largely on clinical evaluations. The objective of this study was to determine whether urinary metabolites are significantly altered post-SRC compared to pre-injury.Setting: Outpatient sports medicine clinic.Participants: Twenty-six male youth sport participants.Methods: Urine was analyzed pre-injury and after SRC by 1H NMR spectroscopy. Data were analyzed using multivariate statistics, pairwise t-test, and metabolic pathway analysis. Variable importance analysis based on random variable combination (VIAVC) was applied to the entire data set and resulted in a panel of 18 features. Partial least square discriminant analysis was performed exploring the separation between pre-injury and post-SRC groups. Pathway topography analysis was completed to identify biological pathway involvement. Spearman correlations provide support for the relationships between symptom burden and length of return to play and quantifiable metabolic changes in the human urinary metabolome.Results: Phenylalanine and 3-indoxysulfate were upregulated, while citrate, propylene glycol, 1-methylhistidine, 3-methylhistidine, anserine, and carnosine were downregulated following SRC. A receiver operator curve (ROC) tool constructed using the 18-feature classifier had an area under the curve (AUC) of 0.887. A pairwise t-test found an additional 19 altered features, 7 of which overlapped with the VIAVC analysis. Pathway topology analysis indicated that aminoacyl-tRNA biosynthesis and beta-alanine metabolism were the two pathways most significantly changed. There was a significant positive correlation between post-SRC 2-hydroxybutyrate and the length of return to play (ρ = 0.482, p = 0.02) as well as the number of symptoms and post-SRC lactose (ρ = 0.422, p = 0.036).Conclusion: We found that 1H NMR metabolomic urinary analysis can identify a set of metabolites that can correctly classify SRC with an accuracy of 81.6%, suggesting potential for a more objective method of characterizing SRC. Correlations to both the number of symptoms and length of return to play indicated that 2-hydroxybutyrate and lactose may have potential applications as biomarkers for sport-related concussion.https://www.frontiersin.org/articles/10.3389/fneur.2021.645829/fullsports-related concussionurine metabolomics1H NMR spectroscopydiagnostic toolbiomarker |
| spellingShingle | Zachary R. Wanner Cormac G. Southam Cormac G. Southam Prachi Sanghavi Naveenjyote S. Boora Eric J. Paxman Sean P. Dukelow Sean P. Dukelow Brian W. Benson Brian W. Benson Tony Montina Gerlinde A. S. Metz Chantel T. Debert Chantel T. Debert Alterations in Urine Metabolomics Following Sport-Related Concussion: A 1H NMR-Based Analysis Frontiers in Neurology sports-related concussion urine metabolomics 1H NMR spectroscopy diagnostic tool biomarker |
| title | Alterations in Urine Metabolomics Following Sport-Related Concussion: A 1H NMR-Based Analysis |
| title_full | Alterations in Urine Metabolomics Following Sport-Related Concussion: A 1H NMR-Based Analysis |
| title_fullStr | Alterations in Urine Metabolomics Following Sport-Related Concussion: A 1H NMR-Based Analysis |
| title_full_unstemmed | Alterations in Urine Metabolomics Following Sport-Related Concussion: A 1H NMR-Based Analysis |
| title_short | Alterations in Urine Metabolomics Following Sport-Related Concussion: A 1H NMR-Based Analysis |
| title_sort | alterations in urine metabolomics following sport related concussion a 1h nmr based analysis |
| topic | sports-related concussion urine metabolomics 1H NMR spectroscopy diagnostic tool biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2021.645829/full |
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