Abstract
BackgroundMore than 230,000 veterans—about 1/3 of US personnel deployed in the 1990–1991 Persian Gulf War—developed chronic, multi-symptom health problems now called “Gulf War illness” (GWI), for which mechanisms and objective diagnostic signatures continue to be sought.MethodsTargeted, broad-spectrum serum metabolomics was used to gain insights into the biology of GWI. 40 male participants, included 20 veterans who met both Kansas and CDC diagnostic criteria for GWI and 20 nonveteran controls without similar symptoms that were 1:1 matched to GWI cases by age, sex, and ethnicity. Serum samples were collected and archived at -80° C prior to testing. 358 metabolites from 46 biochemical pathways were measured by hydrophilic interaction liquid chromatography and tandem mass spectrometry.ResultsVeterans with GWI, compared to healthy controls, had abnormalities in 8 of 46 biochemical pathways interrogated. Lipid abnormalities accounted for 78% of the metabolic impact. Fifteen ceramides and sphingomyelins, and four phosphatidylcholine lipids were increased. Five of the 8 pathways were shared with the previously reported metabolic phenotype of males with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, 4 of the 5 shared pathways were regulated in opposite directions; key pathways that were up-regulated in GWI were down-regulated in ME/CFS. The single pathway regulated in the same direction was purines, which were decreased.ConclusionsOur data show that despite heterogeneous exposure histories, a metabolic phenotype of GWI was clearly distinguished from controls. Metabolomic differences between GWI and ME/CFS show that common clinical symptoms like fatigue can have different chemical mechanisms and different diagnostic implications. Larger studies will be needed to validate these findings.
Highlights
Gulf War illness (GWI) is a complex, multi-organ system condition, affecting about 1/3 of US personnel deployed to the 1990–1991 Persian Gulf War [1], for which no single objective diagnostic test yet exists
More than 230,000 veterans—about 1/3 of US personnel deployed in the 1990–1991 Persian Gulf War—developed chronic, multi-symptom health problems called “Gulf War illness” (GWI), for which mechanisms and objective diagnostic signatures continue to be sought
4 of the 5 shared pathways were regulated in opposite directions; key pathways that were upregulated in GWI were down-regulated in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Summary
Gulf War illness (GWI) is a complex, multi-organ system condition, affecting about 1/3 of US personnel deployed to the 1990–1991 Persian Gulf War [1], for which no single objective diagnostic test yet exists. In 2014, the NAM (under its previous name, the Institute of Medicine) summarized the case definitions that have been used for GWI [2], as listed in Box 1. Box 1: Summary of Diagnostic Criteria for Gulf War Illness. Kansas Criteria [7]: Chronic symptoms in 3 or more of the following 6 domains dating to service in 1990: 1. More than 230,000 veterans—about 1/3 of US personnel deployed in the 1990–1991 Persian Gulf War—developed chronic, multi-symptom health problems called “Gulf War illness” (GWI), for which mechanisms and objective diagnostic signatures continue to be sought
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