Metabolic features of Gulf War illness. (Naviaux 2019)

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PLoS One. 2019 Jul 26;14(7):e0219531. doi: 10.1371/journal.pone.0219531. eCollection 2019.

Metabolic features of Gulf War illness.
Naviaux RK1,2,3,4, Naviaux JC1,5, Li K1,2, Wang L1,2, Monk JM1,2, Bright AT1,2, Koslik HJ6, Ritchie JB6, Golomb BA6.
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Abstract
BACKGROUND:
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 now called "Gulf War illness" (GWI), for which mechanisms and objective diagnostic signatures continue to be sought.

METHODS:
Targeted, 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.

RESULTS:
Veterans 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.

CONCLUSIONS:
Our 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.

PMID: 31348786 DOI: 10.1371/journal.pone.0219531
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Sidny

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Veterans 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.


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It’s a shame how we know so much about what’s going on (metabolically speaking at least) but yet have no real practical curative therapies.
 

perrier

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It’s a shame how we know so much about what’s going on (metabolically speaking at least) but yet have no real practical curative therapies.
The thing is: do we really know what exactly is going on in this illness? For instance, we know that diabetes is due to pancreatic cell destruction or insulin resistance. But as yet we do not seem to know what this ME is due to. I am worried that some doctors think it's a problem with many areas of the body--several illnesses. I hope this is not true.
 

JES

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The thing is: do we really know what exactly is going on in this illness? For instance, we know that diabetes is due to pancreatic cell destruction or insulin resistance. But as yet we do not seem to know what this ME is due to. I am worried that some doctors think it's a problem with many areas of the body--several illnesses. I hope this is not true.
I believe that as per Occam's razor, it's not likely that ME/CFS patients have core issues in all of the different areas of the body where symptoms are reported. It will probably boil down to a relatively small number of root causes. Regarding diabetes, we know what the affected part of the body is, but frustratingly, science doesn't yet know the actual root cause of type 1 diabetes either, although there are some hypotheses. And more frustratingly, with ME/CFS we have neither the exact affected organ nor the root cause.

The currently multidisciplinary efforts of Ron Davis and other US research collaborations are probably best equipped to find actual root cause(s). I believe it has to happen sooner or later simply because technology has improved tremendously. Davis mentioned in some Q&A that they could find HIV within 24 hours using the current technology available, which is pretty impressive.

The Naviaux findings can explain the symptomatology and why ME/CFS or Gulf War illness wreaks havoc on the body, but Naviaux doesn't really attempt to explain the core issue in my view, it's rather an explanation of the downstream metabolic changes. This work is important in itself though in order to find biomarkers to characterize the disease better.
 
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Isn't suramin being trialled by Naviaux at some point to see if it helps the healing cycle not completed in m.e.?
 

pattismith

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Similarities and contrasts with metabolomic features of chronic fatigue syndrome


Five of the 8 pathways that were disturbed in males with GWI have been previously reported to be abnormal in males with ME/CFS [31] (Fig 4). ME/CFS has been reported to be an energy reallocation program and dauer-like multisystem disease that can be triggered by a variety of infectious and environmental agents and injuries [31].
Others have interpreted the bioenergetics of ME/CFS as conserved energy use in the face of reduced energy supply from mitochondria [71].
ME/CFS shares some clinical symptoms with GWI. Shared symptoms include fatigue, sleep problems, and cognitive impairment.
The prevalence of CFS is elevated in veterans with GWI [72], but the disease characteristics are reported to differ from CFS in civilians [5, 73]. For example, a contrasting symptom is post-exertional malaise, which is a defining symptom in ME/CFS [74], but is not defining or prominent in GWI.

When specific metabolites were compared, we found that veterans with GWI and patients with ME/CFS showed the opposite metabolic abnormalities in 4 of 5 shared pathways (Fig 4 red shaded pathways, Table 6) [2, 74]. The only pathway that was regulated in the same direction (down in both) was purine metabolism (Tables (Tables33 and and6,6, Fig 4). In addition to their broad intracellular roles as intermediates and energy carriers for metabolism, extracellular purines and pyrimidines play a critical role in purinergic signaling for regulation of energy homeostasis [75], the control of chronic pain and inflammation [76], and regulate healing [66]. Altered plasma purine pools may reflect systemic alternations in purinergic signaling [77] associated with mitochondrial metabolism, healing, and the cell danger response [54, 66, 78]

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Metabolic similarities and differences between Gulf War illness and chronic fatigue syndrome.
Four of five pathways shared by males with GWI and CFS were regulated in opposite directions (red font). Only purines were regulated in the same direction—decreased in both GWI and CFS. *One GWI pathway (endocannabinoids) was similarly decreased in females with CFS, but not in males with CFS