scholarly journals Obesity Worsens Gulf War Illness Symptom Persistence Pathology by Linking Altered Gut Microbiome Species to Long-Term Gastrointestinal, Hepatic, and Neuronal Inflammation in a Mouse Model

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2764
Author(s):  
Dipro Bose ◽  
Punnag Saha ◽  
Ayan Mondal ◽  
Brian Fanelli ◽  
Ratanesh K. Seth ◽  
...  
Keyword(s):  
Chemical Exposure ◽  
Chronic Fatigue ◽  
Gulf War ◽  
Western Diet ◽  
Post Traumatic Stress ◽  
Metabolic Disturbances ◽  
Gulf War Illness ◽  
Increased Risk ◽  
Obese Phenotype ◽  
Symptom Persistence

Persistence of Gulf War illness (GWI) pathology among deployed veterans is a clinical challenge even after almost three decades. Recent studies show a higher prevalence of obesity and metabolic disturbances among Gulf War veterans primarily due to the existence of post-traumatic stress disorder (PTSD), chronic fatigue, sedentary lifestyle, and consumption of a high-carbohydrate/high-fat diet. We test the hypothesis that obesity from a Western-style diet alters host gut microbial species and worsens gastrointestinal and neuroinflammatory symptom persistence. We used a 5 month Western diet feeding in mice that received prior Gulf War (GW) chemical exposure to mimic the home phase obese phenotype of the deployed GW veterans. The host microbial profile in the Western diet-fed GWI mice showed a significant decrease in butyrogenic and immune health-restoring bacteria. The altered microbiome was associated with increased levels of IL6 in the serum, Claudin-2, IL6, and IL1β in the distal intestine with concurrent inflammatory lesions in the liver and hyperinsulinemia. Microbial dysbiosis was also associated with frontal cortex levels of increased IL6 and IL1β, activated microglia, decreased levels of brain derived neurotrophic factor (BDNF), and higher accumulation of phosphorylated Tau, an indicator of neuroinflammation-led increased risk of cognitive deficiencies. Mechanistically, serum from Western diet-fed mice with GWI significantly increased microglial activation in transformed microglial cells, increased tyrosyl radicals, and secreted IL6. Collectively, the results suggest that an existing obese phenotype in GWI worsens persistent gastrointestinal and neuronal inflammation, which may contribute to poor outcomes in restoring cognitive function and resolving fatigue, leading to the deterioration of quality of life.

scholarly journals Host Akkermansia muciniphila Abundance Correlates With Gulf War Illness Symptom Persistence via NLRP3-Mediated Neuroinflammation and Decreased Brain-Derived Neurotrophic Factor

2020 ◽  
Vol 15 ◽  
pp. 263310552094248 ◽  
Author(s):  
Diana Kimono ◽  
Dipro Bose ◽  
Ratanesh K Seth ◽  
Ayan Mondal ◽  
Punnag Saha ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Neurological Disorders ◽  
Chemical Exposure ◽  
Gulf War ◽  
Inflammasome Activation ◽  
Barrier Dysfunction ◽  
Gulf War Illness ◽  
Nlrp3 Gene ◽  
Akkermansia Muciniphila ◽  
Symptom Persistence

Neurological disorders are commonly reported among veterans who returned from the Gulf war. Veterans who suffer from Gulf War illness (GWI) complain of continued symptom persistence that includes neurological disorders, muscle weakness, headaches, and memory loss, that developed during or shortly after the war. Our recent research showed that chemical exposure associated microbial dysbiosis accompanied by a leaky gut connected the pathologies in the intestine, liver, and brain. However, the mechanisms that caused the symptoms to persist even 30 years after the war remained elusive to investigators. In this study, we used a rodent model of GWI to investigate the persistence of microbiome alterations, resultant chronic inflammation, and its effect on neurotrophic and synaptic plasticity marker BDNF. The results showed that exposure to GW chemicals (the pesticide permethrin and prophylactic drug pyridostigmine bromide) resulted in persistent pathology characterized by the low relative abundance of the probiotic bacteria Akkermansia muciniphila in the gut, which correlated with high circulatory HMGB1 levels, blood-brain barrier dysfunction, neuroinflammation and lowered neurotrophin BDNF levels. Mechanistically, we used mice lacking the NLRP3 gene to investigate this inflammasome’s role in observed pathology. These mice had significantly decreased inflammation and a subsequent increase in BDNF in the frontal cortex. This suggests that a persistently low species abundance of Akkermansia muciniphila and associated chronic inflammation due to inflammasome activation might be playing a significant role in contributing to chronic neurological problems in GWI. A therapeutic approach with various small molecules that can target both the restoration of a healthy microbiome and decreasing inflammasome activation might have better outcomes in treating GWI symptom persistence.

scholarly journals Post-traumatic stress impact on health outcomes in Gulf War Illness

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Mary Jeffrey ◽  
Fanny Collado ◽  
Jeffrey Kibler ◽  
Christian DeLucia ◽  
Steven Messer ◽  
...  
Keyword(s):  
Health Outcomes ◽  
Short Form ◽  
Gulf War ◽  
Ptsd Symptoms ◽  
Symptom Presentation ◽  
Trauma Symptoms ◽  
Post Traumatic Stress ◽  
Gulf War Illness ◽  
Cut Point ◽  
Wide Range

Abstract Background Gulf War Illness (GWI) is a chronic, multi-symptomatic disorder affecting an estimated 25–32% of the returning military veterans of the 1990–1991 Persian Gulf War. GWI presents with a wide range of symptoms including fatigue, muscle pain, cognitive problems, insomnia, rashes and gastrointestinal issues and continues to be a poorly understood illness. This heterogeneity of GWI symptom presentation complicates diagnosis as well as the identification of effective treatments. Defining subgroups of the illness may help alleviate these complications. Our aim is to determine if GWI can be divided into distinct subgroups based on PTSD symptom presentation. Methods Veterans diagnosed with GWI (n = 47) and healthy sedentary veteran controls (n = 52) were recruited through the Miami Affairs (VA) Medical Health Center. Symptoms were assessed via the RAND short form health survey (36), the multidimensional fatigue inventory, and the Davidson trauma scale. Hierarchal regression modeling was performed on measures of health and fatigue with PTSD symptoms as a covariate. This was followed by univariate analyses conducted with two separate GWI groups based on a cut-point of 70 for their total Davidson Trauma Scale value and performing heteroscedastic t-tests across all measures. Results Overall analyses returned two symptom-based subgroups differing significantly across all health and trauma symptoms. These subgroups supported PTSD symptomatology as a means to subgroup veterans. Hierarchical models showed that GWI and levels of PTSD symptoms both impact measures of physical, social, and emotional consequences of poor health (ΔR2 = 0.055–0.316). However, GWI appeared to contribute more to fatigue measures. Cut-point analysis retained worse health outcomes across all measures for GWI with PTSD symptoms compared to those without PTSD symptoms, and healthy controls. Significant differences were observed in mental and emotional measures. Conclusions Therefore, this research supports the idea that comorbid GWI and PTSD symptoms lead to worse health outcomes, while demonstrating how GWI and PTSD symptoms may uniquely contribute to clinical presentation.

scholarly journals Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls

2020 ◽  
Vol 10 (9) ◽  
pp. 610
Author(s):  
Mohamed B. Abou-Donia ◽  
Elizabeth S. Lapadula ◽  
Maxine H. Krengel ◽  
Emily Quinn ◽  
Jessica LeClair ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Chronic Fatigue ◽  
Alpha Synuclein ◽  
Gulf War ◽  
Gulf War Illness ◽  
Control Groups ◽  
Neurofilament Protein ◽  
Diagnostic Characteristics ◽  
Cns Proteins

For the past 30 years, there has been a lack of objective tools for diagnosing Gulf War Illness (GWI), which is largely characterized by central nervous system (CNS) symptoms emerging from 1991 Gulf War (GW) veterans. In a recent preliminary study, we reported the presence of autoantibodies against CNS proteins in the blood of veterans with GWI, suggesting a potential objective biomarker for the disorder. Now, we report the results of a larger, confirmatory study of these objective biomarkers in 171 veterans with GWI compared to 60 healthy GW veteran controls and 85 symptomatic civilian controls (n = 50 myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and n = 35 irritable bowel syndrome (IBS)). Specifically, we compared plasma markers of CNS autoantibodies for diagnostic characteristics of the four groups (GWI, GW controls, ME/CFS, IBS). For veterans with GWI, the results showed statistically increased levels of nine of the ten autoantibodies against neuronal “tubulin, neurofilament protein (NFP), Microtubule Associated Protein-2 (MAP-2), Microtubule Associated Protein-Tau (Tau), alpha synuclein (α-syn), calcium calmodulin kinase II (CaMKII)” and glial proteins “Glial Fibrillary Acidic Protein (GFAP), Myelin Associated Glycoprotein (MAG), Myelin Basic Protein (MBP), S100B” compared to healthy GW controls as well as civilians with ME/CFS and IBS. Next, we summed all of the means of the CNS autoantibodies for each group into a new index score called the Neurodegeneration Index (NDI). The NDI was calculated for each tested group and showed veterans with GWI had statistically significantly higher NDI values than all three control groups. The present study confirmed the utility of the use of plasma autoantibodies for CNS proteins to distinguish among veterans with GWI and other healthy and symptomatic control groups.

scholarly journals A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome

2013 ◽  
Vol 14 (1) ◽  
pp. 29 ◽  
Author(s):  
Anne Smylie ◽  
Gordon Broderick ◽  
Henrique Fernandes ◽  
Shirin Razdan ◽  
Zachary Barnes ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Chronic Fatigue ◽  
Gulf War ◽  
Gulf War Illness ◽  
Fatigue Syndrome ◽  
Immune Signatures
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