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Urinary Metabolites as Predictors of Acute Mountain Sickness Severity

Individuals sojourning at high altitude (≥2,500m) often develop acute mountain sickness (AMS). However, substantial unexplained inter-individual variability in AMS severity exists. Untargeted metabolomics assays are increasingly used to identify novel biomarkers of susceptibility to illness, and to...

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Autores principales: Sibomana, Isaie, Foose, Daniel P., Raymer, Michael L., Reo, Nicholas V., Karl, J. Philip, Berryman, Claire E., Young, Andrew J., Pasiakos, Stefan M., Mauzy, Camilla A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475947/
https://www.ncbi.nlm.nih.gov/pubmed/34588992
http://dx.doi.org/10.3389/fphys.2021.709804
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author Sibomana, Isaie
Foose, Daniel P.
Raymer, Michael L.
Reo, Nicholas V.
Karl, J. Philip
Berryman, Claire E.
Young, Andrew J.
Pasiakos, Stefan M.
Mauzy, Camilla A.
author_facet Sibomana, Isaie
Foose, Daniel P.
Raymer, Michael L.
Reo, Nicholas V.
Karl, J. Philip
Berryman, Claire E.
Young, Andrew J.
Pasiakos, Stefan M.
Mauzy, Camilla A.
author_sort Sibomana, Isaie
collection PubMed
description Individuals sojourning at high altitude (≥2,500m) often develop acute mountain sickness (AMS). However, substantial unexplained inter-individual variability in AMS severity exists. Untargeted metabolomics assays are increasingly used to identify novel biomarkers of susceptibility to illness, and to elucidate biological pathways linking environmental exposures to health outcomes. This study used untargeted nuclear magnetic resonance (NMR)-based metabolomics to identify urine metabolites associated with AMS severity during high altitude sojourn. Following a 21-day stay at sea level (SL; 55m), 17 healthy males were transported to high altitude (HA; 4,300m) for a 22-day sojourn. AMS symptoms measured twice daily during the first 5days at HA were used to dichotomize participants according to AMS severity: moderate/severe AMS (AMS; n=11) or no/mild AMS (NoAMS; n=6). Urine samples collected on SL day 12 and HA days 1 and 18 were analyzed using proton NMR tools and the data were subjected to multivariate analyses. The SL urinary metabolite profiles were significantly different (p≤0.05) between AMS vs. NoAMS individuals prior to high altitude exposure. Differentially expressed metabolites included elevated levels of creatine and acetylcarnitine, and decreased levels of hypoxanthine and taurine in the AMS vs. NoAMS group. In addition, the levels of two amino acid derivatives (4-hydroxyphenylpyruvate and N-methylhistidine) and two unidentified metabolites (doublet peaks at 3.33ppm and a singlet at 8.20ppm) were significantly different between groups at SL. By HA day 18, the differences in urinary metabolites between AMS and NoAMS participants had largely resolved. Pathway analysis of these differentially expressed metabolites indicated that they directly or indirectly play a role in energy metabolism. These observations suggest that alterations in energy metabolism before high altitude exposure may contribute to AMS susceptibility at altitude. If validated in larger cohorts, these markers could inform development of a non-invasive assay to screen individuals for AMS susceptibility prior to high altitude sojourn.
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spelling pubmed-84759472021-09-28 Urinary Metabolites as Predictors of Acute Mountain Sickness Severity Sibomana, Isaie Foose, Daniel P. Raymer, Michael L. Reo, Nicholas V. Karl, J. Philip Berryman, Claire E. Young, Andrew J. Pasiakos, Stefan M. Mauzy, Camilla A. Front Physiol Physiology Individuals sojourning at high altitude (≥2,500m) often develop acute mountain sickness (AMS). However, substantial unexplained inter-individual variability in AMS severity exists. Untargeted metabolomics assays are increasingly used to identify novel biomarkers of susceptibility to illness, and to elucidate biological pathways linking environmental exposures to health outcomes. This study used untargeted nuclear magnetic resonance (NMR)-based metabolomics to identify urine metabolites associated with AMS severity during high altitude sojourn. Following a 21-day stay at sea level (SL; 55m), 17 healthy males were transported to high altitude (HA; 4,300m) for a 22-day sojourn. AMS symptoms measured twice daily during the first 5days at HA were used to dichotomize participants according to AMS severity: moderate/severe AMS (AMS; n=11) or no/mild AMS (NoAMS; n=6). Urine samples collected on SL day 12 and HA days 1 and 18 were analyzed using proton NMR tools and the data were subjected to multivariate analyses. The SL urinary metabolite profiles were significantly different (p≤0.05) between AMS vs. NoAMS individuals prior to high altitude exposure. Differentially expressed metabolites included elevated levels of creatine and acetylcarnitine, and decreased levels of hypoxanthine and taurine in the AMS vs. NoAMS group. In addition, the levels of two amino acid derivatives (4-hydroxyphenylpyruvate and N-methylhistidine) and two unidentified metabolites (doublet peaks at 3.33ppm and a singlet at 8.20ppm) were significantly different between groups at SL. By HA day 18, the differences in urinary metabolites between AMS and NoAMS participants had largely resolved. Pathway analysis of these differentially expressed metabolites indicated that they directly or indirectly play a role in energy metabolism. These observations suggest that alterations in energy metabolism before high altitude exposure may contribute to AMS susceptibility at altitude. If validated in larger cohorts, these markers could inform development of a non-invasive assay to screen individuals for AMS susceptibility prior to high altitude sojourn. Frontiers Media S.A. 2021-09-13 /pmc/articles/PMC8475947/ /pubmed/34588992 http://dx.doi.org/10.3389/fphys.2021.709804 Text en Copyright © 2021 Sibomana, Foose, Raymer, Reo, Karl, Berryman, Young, Pasiakos and Mauzy. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Sibomana, Isaie
Foose, Daniel P.
Raymer, Michael L.
Reo, Nicholas V.
Karl, J. Philip
Berryman, Claire E.
Young, Andrew J.
Pasiakos, Stefan M.
Mauzy, Camilla A.
Urinary Metabolites as Predictors of Acute Mountain Sickness Severity
title Urinary Metabolites as Predictors of Acute Mountain Sickness Severity
title_full Urinary Metabolites as Predictors of Acute Mountain Sickness Severity
title_fullStr Urinary Metabolites as Predictors of Acute Mountain Sickness Severity
title_full_unstemmed Urinary Metabolites as Predictors of Acute Mountain Sickness Severity
title_short Urinary Metabolites as Predictors of Acute Mountain Sickness Severity
title_sort urinary metabolites as predictors of acute mountain sickness severity
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475947/
https://www.ncbi.nlm.nih.gov/pubmed/34588992
http://dx.doi.org/10.3389/fphys.2021.709804
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