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      The metabolic recovery of marathon runners: an untargeted 1H-NMR metabolomics perspective

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          Abstract

          Introduction: Extreme endurance events may result in numerous adverse metabolic, immunologic, and physiological perturbations that may diminish athletic performance and adversely affect the overall health status of an athlete, especially in the absence of sufficient recovery. A comprehensive understanding of the post-marathon recovering metabolome, may aid in the identification of new biomarkers associated with marathon-induced stress, recovery, and adaptation, which can facilitate the development of improved training and recovery programs and personalized monitoring of athletic health/recovery/performance. Nevertheless, an untargeted, multi-disciplinary elucidation of the complex underlying biochemical mechanisms involved in recovery after such an endurance event is yet to be demonstrated.

          Methods: This investigation employed an untargeted proton nuclear magnetic resonance metabolomics approach to characterize the post-marathon recovering metabolome by systematically comparing the pre-, immediately post, 24, and 48 h post-marathon serum metabolite profiles of 15 athletes.

          Results and Discussion: A total of 26 metabolites were identified to fluctuate significantly among post-marathon and recovery time points and were mainly attributed to the recovery of adenosine triphosphate, redox balance and glycogen stores, amino acid oxidation, changes to gut microbiota, and energy drink consumption during the post-marathon recovery phase. Additionally, metabolites associated with delayed-onset muscle soreness were observed; however, the mechanisms underlying this commonly reported phenomenon remain to be elucidated. Although complete metabolic recovery of the energy-producing pathways and fuel substrate stores was attained within the 48 h recovery period, several metabolites remained perturbed throughout the 48 h recovery period and/or fluctuated again following their initial recovery to pre-marathon-related levels.

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          Most cited references75

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          MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights

          Since its first release over a decade ago, the MetaboAnalyst web-based platform has become widely used for comprehensive metabolomics data analysis and interpretation. Here we introduce MetaboAnalyst version 5.0, aiming to narrow the gap from raw data to functional insights for global metabolomics based on high-resolution mass spectrometry (HRMS). Three modules have been developed to help achieve this goal, including: (i) a LC–MS Spectra Processing module which offers an easy-to-use pipeline that can perform automated parameter optimization and resumable analysis to significantly lower the barriers to LC-MS1 spectra processing; (ii) a Functional Analysis module which expands the previous MS Peaks to Pathways module to allow users to intuitively select any peak groups of interest and evaluate their enrichment of potential functions as defined by metabolic pathways and metabolite sets; (iii) a Functional Meta-Analysis module to combine multiple global metabolomics datasets obtained under complementary conditions or from similar studies to arrive at comprehensive functional insights. There are many other new functions including weighted joint-pathway analysis, data-driven network analysis, batch effect correction, merging technical replicates, improved compound name matching, etc. The web interface, graphics and underlying codebase have also been refactored to improve performance and user experience. At the end of an analysis session, users can now easily switch to other compatible modules for a more streamlined data analysis. MetaboAnalyst 5.0 is freely available at https://www.metaboanalyst.ca . Graphical Abstract From raw data to statistical and functional insights using MetaboAnalyst 5.0.
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            Exercise metabolism and the molecular regulation of skeletal muscle adaptation.

            Preservation of aerobic fitness and skeletal muscle strength through exercise training can ameliorate metabolic dysfunction and prevent chronic disease. These benefits are mediated in part by extensive metabolic and molecular remodeling of skeletal muscle by exercise. Aerobic and resistance exercise represent extremes on the exercise continuum and elicit markedly different training responses that are mediated by a complex interplay between a myriad of signaling pathways coupled to downstream regulators of transcription and translation. Here, we review the metabolic responses and molecular mechanisms that underpin the adaptatation of skeletal muscle to acute exercise and exercise training. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Untargeted Metabolomics Strategies—Challenges and Emerging Directions

              Metabolites are building blocks of cellular function. These species are involved in enzyme-catalyzed chemical reactions and are essential for cellular function. Upstream biological disruptions result in a series of metabolomic changes, and as such the metabolome holds a wealth of information that is thought to be most predictive of phenotype. Uncovering this knowledge is a work in progress. The field of metabolomics is still maturing; the community has leveraged proteomics experience when applicable and developed a range of sample preparation and instrument methodology along with myriad data processing and analysis approaches. Research focuses have now shifted toward a fundamental understanding of the biology responsible for metabolomic changes. There are several types of metabolomics experiments including both targeted and untargeted analyses. While untargeted, hypothesis generating, workflows exhibit many valuable attributes, challenges inherent to the approach remain. This Critical Insight comments on these challenges, focusing on the identification process of LC-MS based untargeted metabolomics studies – specifically in mammalian systems. Biological interpretation of metabolomics data hinges on the ability to accurately identify metabolites. The range of confidence associated with identifications that is often overlooked is reviewed, and opportunities for advancing the metabolomics field are described.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                04 May 2023
                2023
                : 14
                : 1117687
                Affiliations
                [1] 1 Human Metabolomics , Department of Biochemistry , Faculty of Natural and Agricultural Sciences , North-West University , Potchefstroom, South Africa
                [2] 2 Department of Sport Exercise and Nutrition , School of Science and Computing , Atlantic Technological University , Galway, Ireland
                [3] 3 Department of Sport, Exercise and Rehabilitation , Faculty of Health and Life Sciences , Northumbria University , Newcastle upon Tyne, United Kingdom
                [4] 4 Water Research Group , School of Environmental Sciences and Development , North-West University , Potchefstroom, South Africa
                [5] 5 School of Sport, Exercise and Health Sciences , Loughborough University , Loughborough, United Kingdom
                [6] 6 Human and Exercise Nutrition Research Centre , School of Biomedical, Nutritional and Sport Sciences , Faculty of Medical Sciences , Newcastle University , Newcastle upon Tyne, United Kingdom
                Author notes

                Edited by: Jan Jacek Kaczor, University of Gdansk, Poland

                Reviewed by: Ivan Cuk, University of Belgrade, Serbia

                Sina Kistner, Max Rubner Institute Karlsruhe, Germany

                *Correspondence: Du Toit Loots, dutoit.loots@ 123456nwu.ac.za
                Article
                1117687
                10.3389/fphys.2023.1117687
                10192615
                0cf4473a-5fd3-48cf-b774-8ad5133a2607
                Copyright © 2023 Bester, Stander, Mason, Keane, Howatson, Clifford, Stevenson and Loots.

                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.

                History
                : 06 December 2022
                : 20 April 2023
                Categories
                Physiology
                Original Research
                Custom metadata
                Exercise Physiology

                Anatomy & Physiology
                metabolomics,metabolism,marathon,1h-nmr spectroscopy,recovery,endurance running,delayed onset muscle soreness (doms)

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