Evidence for Somatic Hypersensitivity in Veterans With Gulf War Illness and Gastrointestinal Symptoms

Zhou, QiQi; Verne, Meghan L; Zhang, Buyi; Verne, G. Nicholas

doi:10.1097/ajp.0000000000000611

Cited by 16 publications

(12 citation statements)

References 41 publications

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“…In our pilot study, we found that the GWI+GI group reported much higher symptom burden for pain (McGill Pain Scale), fatigue (MFI-20) and sleep (PSQI) on validated measures compared with both the GWI-GI and control groups. These finding also correspond with prior studies reporting lower pain thresholds in GW veterans with GI in other study cohorts suggesting that a targeted approach of treating inflammatory mediators in GWI+GI could potentially reduce other chronic health symptoms [22,23,24].…”

Section: Discussionsupporting

confidence: 90%

“…Only more recently has attention started to turn toward understanding the relationship between CNS effects and other debilitating symptoms including GI disturbances and chronic pain experienced by GW veterans. Veterans with GWI report experiencing numerous chronic GI symptoms including; abdominal pain/discomfort, bloating, nausea, vomiting, diarrhea as well as a clinical diagnosis of Irritable Bowel Syndrome (IBS) in many cases [22,23,24]. Our group has recently demonstrated the role of the gut microbiome in a mouse model of GWI on the gut microbiome-brain axis and the enteric nervous system [16,25,26].…”

Section: Introductionmentioning

confidence: 99%

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The Gut-Microbiome in Gulf War Veterans: A Preliminary Report

Janulewicz

Seth

Carlson

et al. 2019

IJERPH

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Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting the central nervous system (CNS), immune and gastrointestinal (GI) systems of Gulf War veterans (GWV). We assessed the relationships between GWI, GI symptoms, gut microbiome and inflammatory markers in GWV from the Boston Gulf War Illness Consortium (GWIC). Three groups of GWIC veterans were recruited in this pilot study; GWV without GWI and no gastrointestinal symptoms (controls), GWV with GWI and no gastrointestinal symptoms (GWI-GI), GWV with GWI who reported gastrointestinal symptoms (GW+GI). Here we report on a subset of the first thirteen stool samples analyzed. Results showed significantly different gut microbiome patterns among the three groups and within the GWI +/−GI groups. Specifically, GW controls had a greater abundance of firmicutes and the GWI+GI group had a greater abundance of the phyla bacteroidetes, actinobacteria, euryarchaeota, and proteobacteria as well as higher abundances of the families Bacteroidaceae, Erysipelotrichaceae, and Bifidobacteriaceae. The GWI+GI group also showed greater plasma levels of the inflammatory cytokine TNF-RI and they endorsed significantly more chemical weapons exposure during the war and reported significantly greater chronic pain, fatigue and sleep difficulties than the other groups. Studies with larger samples sizes are needed to confirm these initial findings.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

The Gut-Microbiome in Gulf War Veterans: A Preliminary Report

Janulewicz

Seth

Carlson

et al. 2019

IJERPH

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“…According to Coker et al (1999), the most commonly reported gastrointestinal issues reported among United States and British Gulf war (GW) veterans were diarrhea, vomiting, and stomach problems. A study by Dunphy et al (2003) showed veterans of the Persian GW presented with diarrhea and had rectal hypersensitivity as did Zhou et al (2018) who reported increased somatic hypersensitivity and pain among some GW veterans with GI issues.…”

Section: Introductionmentioning

confidence: 99%

Dysbiosis-Associated Enteric Glial Cell Immune-Activation and Redox Imbalance Modulate Tight Junction Protein Expression in Gulf War Illness Pathology

et al. 2019

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About 14% of veterans who suffer from Gulf war illness (GWI) complain of some form of gastrointestinal disorder but with no significant markers of clinical pathology. Our previous studies have shown that exposure to GW chemicals resulted in altered microbiome which was associated with damage associated molecular pattern (DAMP) release followed by neuro and gastrointestinal inflammation with loss of gut barrier integrity. Enteric glial cells (EGC) are emerging as important regulators of the gastrointestinal tract and have been observed to change to a reactive phenotype in several functional gastrointestinal disorders such as IBS and IBD. This study is aimed at investigating the role of dysbiosis associated EGC immune-activation and redox instability in contributing to observed gastrointestinal barrier integrity loss in GWI via altered tight junction protein expression. Using a mouse model of GWI and in vitro studies with cultured EGC and use of antibiotics to ensure gut decontamination we show that exposure to GW chemicals caused dysbiosis associated change in EGCs. EGCs changed to a reactive phenotype characterized by activation of TLR4-S100β/RAGE-iNOS pathway causing release of nitric oxide and activation of NOX2 since gut sterility with antibiotics prevented this change. The resulting peroxynitrite generation led to increased oxidative stress that triggered inflammation as shown by increased NLRP-3 inflammasome activation and increased cell death. Activated EGCs in vivo and in vitro were associated with decrease in tight junction protein occludin and selective water channel aquaporin-3 with a concomitant increase in Claudin-2. The tight junction protein levels were restored following a parallel treatment of GWI mice with a TLR4 inhibitor SsnB and butyric acid that are known to decrease the immunoactivation of EGCs. Our study demonstrates that immune-redox mechanisms in EGC are important players in the pathology in GWI and may be possible therapeutic targets for improving outcomes in GWI symptom persistence.

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“…The study by Zhou et al [61] reports somatic hypersensitivity in veterans with GWI and with GI symptoms. This study recruited previously deployed GW veterans who reported GI symptoms (n = 53), veteran controls (n = 38) and veterans who had GWI but not GI issues.…”

Section: Enteric Nervous System Dysfunction As a Potentiator Of Inflammationmentioning

confidence: 99%

Gastrointestinal problems, mechanisms and possible therapeutic directions in Gulf war illness: a mini review

Kimono

2021

Military Med Res

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By its nature, Gulf war illness (GWI) is multisymptomatic and affects several organ systems in the body. Along with other symptoms, veterans who suffer from GWI commonly report chronic gastrointestinal issues such as constipation, pain, indigestion, etc. However, until recently, most attention has been focused on neurological disturbances such as cognitive impairments, chronic fatigue, and chronic pain among affected veterans. With such high prevalence of gastrointestinal problems among Gulf war (GW) veterans, it is surprising that there is little research to investigate the mechanisms behind these issues. This review summarizes all the available works on the mechanisms behind gastrointestinal problems in GWI that have been published to date in various databases. Generally, these studies, which were done in rodent models, in vitro and human cohorts propose that an altered microbiome, a reactive enteric nervous system or a leaky gut among other possible mechanisms are the major drivers of gastrointestinal problems reported in GWI. This review aims to draw attention to the gastrointestinal tract as an important player in GWI disease pathology and a potential therapeutic target.

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Evidence for Somatic Hypersensitivity in Veterans With Gulf War Illness and Gastrointestinal Symptoms

Cited by 16 publications

References 41 publications

The Gut-Microbiome in Gulf War Veterans: A Preliminary Report

The Gut-Microbiome in Gulf War Veterans: A Preliminary Report

Dysbiosis-Associated Enteric Glial Cell Immune-Activation and Redox Imbalance Modulate Tight Junction Protein Expression in Gulf War Illness Pathology

Gastrointestinal problems, mechanisms and possible therapeutic directions in Gulf war illness: a mini review

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