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Patterns of serum metabolites in ME\/CFS and GWI are different from control groups and suggest potential dysfunction of energy and lipid metabolism. The metabolomics of cerebrospinal fluid was contrasted between ME\/CFS, GWI and sedentary controls in 2 sets of subjects who had lumbar punctures after either (a) rest or (b) submaximal exercise stress tests. Postexercise GWI and control subjects were subdivided according to acquired transient postexertional postural tachycardia. Banked cerebrospinal fluid specimens were assayed using Biocrates AbsoluteIDQ\u00ae p180 kits for quantitative targeted metabolomics studies of amino acids, amines, acylcarnitines, sphingolipids, lysophospholipids, alkyl and ether phosphocholines. Glutamate was significantly higher in the subgroup of postexercise GWI subjects who did not develop postural tachycardia after exercise compared to nonexercise and other postexercise groups. The only difference between nonexercise groups was higher lysoPC a C28:0 in GWI than ME\/CFS suggesting this biochemical or phospholipase activities may have potential as a biomarker to distinguish between the 2 diseases. Exercise effects were suggested by elevation of short chain acylcarnitine C5-OH (C3-DC-M) in postexercise controls compared to nonexercise ME\/CFS. Limitations include small subgroup sample sizes and absence of postexercise ME\/CFS specimens. Mechanisms of glutamate neuroexcitotoxicity may contribute to neuropathology and \u201cneuroinflammation\u201d in the GWI subset who did not develop postural tachycardia after exercise. Dysfunctional lipid metabolism may distinguish the predominantly female ME\/CFS group from predominantly male GWI subjects.<\/jats:p>","DOI":"10.1371\/journal.pone.0244116","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T23:04:10Z","timestamp":1610579050000},"page":"e0244116","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Exercise modifies glutamate and other metabolic biomarkers in cerebrospinal fluid from Gulf War Illness and Myalgic encephalomyelitis \/ Chronic Fatigue Syndrome"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1866-4177","authenticated-orcid":true,"given":"James N.","family":"Baraniuk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"Kern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaishnavi","family":"Narayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrita","family":"Cheema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"key":"pone.0244116.ref001","doi-asserted-by":"crossref","first-page":"953","DOI":"10.7326\/0003-4819-121-12-199412150-00009","article-title":"The chronic fatigue syndrome: a comprehensive approach to its definition and study. 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