Host gut microbiome and potential therapeutics in Gulf War Illness: A short review

IntroductionApproximately 25%–35% of the 1991 Gulf War Veteran population report symptoms consistent with Gulf War Illness (GWI), a chronic, multi-symptom illness characterised by fatigue, pain, irritable bowel syndrome and problems with cognitive function. GWI is a disabling problem for Gulf War Veterans, and there remains a critical need to identify innovative, novel therapies.Gut microbiota perturbation plays a key role in the symptomatology of other chronic multi-symptom illnesses, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Given similarities between ME/CFS and GWI and the presence of gastrointestinal disorders in GWI patients, Veterans with GWI may also have gut abnormalities like those seen with ME/CFS. In this longitudinal cohort study, we are comparing the diversity (structure) and the metagenomes (function) of the gut microbiome between Gulf War Veterans with and without GWI. If we find differences in Veterans with GWI, the microbiome could be a target for therapeutic intervention to alleviate GWI symptoms.Methods and analysisParticipants answer questions about diet, exercise and lifestyle factors. Participants also complete a questionnaire (based on the Kansas case definition of GWI) regarding their medical history and symptoms; we use this questionnaire to group participants into GWI versus healthy control cohorts. We plan to enrol 52 deployed Gulf War Veterans: 26 with GWI and 26 healthy controls. Participants provide stool and saliva samples weekly for an 8-week period for microbiome analyses. Participants also provide blood samples at the beginning and end of this period, which we will use to compare measures of inflammation markers between the groups.Ethics and disseminationThe protocol was approved by the University of Wisconsin-Madison Health Sciences Institutional Review Board and the William S. Middleton Memorial Veterans Hospital Research and Development Committee. Results of this study will be submitted for publication in a peer-reviewed journal.

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Minocycline Alleviate A Rat Model Of Gulf War Illness Via Altering Gut Microbiome, Attenuating Neuroinflammation And Enhancing Hippocampal Neurogenesis

10.21203/rs.3.rs-45452/v1 ◽

2020 ◽

Author(s):

Liang Liu ◽

Er-Qiang Wang ◽

Cheng Du ◽

Hui-Sheng Chen ◽

Yan Lv

Keyword(s):

Gut Microbiota ◽

Rat Model ◽

Gut Microbiome ◽

Forced Swim Test ◽

Chemical Exposure ◽

Gulf War ◽

Hippocampal Neurogenesis ◽

Gulf War Illness ◽

Object Recognition Test ◽

Minocycline Treatment

Abstract Background: Accumulating evidence suggests that deficits in neurogenesis, chronic inflammation and gut microbiome dysregulation contribute to the pathophysiology of Gulf War Illness (GWI). Minocycline has been demonstrated to be a potent neuroprotective agent and could regulate neuroinflammation. The present study intended to investigate whether treatment of minocycline maintain better cognition and mood function in a rat model of GWI and the potential mechanism. Methods: Rats received 28 days of GWI-related chemical exposure and restraint stress, along with daily minocycline or vehicle treatment. Cognitive and mood function, neuroinflammation, neurogenesis and gut microbiota were detected.Results: We found that minocycline treatment induced better cognitive and mood function in a GWI rat model, as indicated by open-field test, elevated plus maze test, novel object recognition test and forced swim test. Moreover, minocycline treatment reversed the altered gut microbiome, neuroinflammation and the decreased hippocampal neurogenesis of rats with GWI. Conclusion: Taken together, our study indicated that minocycline treatment exerts better cognitive and mood function in GWI rat model, which is possible related to gut microbiota remodeling, restrained inflammation and enhanced hippocampal neurogenesis. These results may establish minocycline a potential prophylactic or therapeutic agent for the treatment of GWI.

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Minocycline alleviates Gulf War Illness rats via altering gut microbiome, attenuating neuroinflammation and enhancing hippocampal neurogenesis

Behavioural Brain Research ◽

10.1016/j.bbr.2021.113366 ◽

2021 ◽

pp. 113366

Author(s):

Liang Liu ◽

Er-Qiang Wang ◽

Cheng Du ◽

Hui-Sheng Chen ◽

Yan Lv

Keyword(s):

Gut Microbiome ◽

Gulf War ◽

Hippocampal Neurogenesis ◽

Gulf War Illness

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Effects of minocycline on neuroinflammation, gut microbiome and hippocampal neurogenesis in rats with Gulf War Illness

10.21203/rs.3.rs-52956/v1 ◽

2020 ◽

Author(s):

Liang Liu ◽

Er-Qiang Wang ◽

Cheng Du ◽

Hui-Sheng Chen ◽

Yan Lv

Keyword(s):

Gut Microbiota ◽

Rat Model ◽

Gut Microbiome ◽

Forced Swim Test ◽

Chemical Exposure ◽

Gulf War ◽

Hippocampal Neurogenesis ◽

Gulf War Illness ◽

Object Recognition Test ◽

Minocycline Treatment

Abstract Background Accumulating evidence suggests that deficits in neurogenesis, chronic inflammation and gut microbiome dysregulation contribute to the pathophysiology of Gulf War Illness (GWI). Minocycline has been demonstrated to be a potent neuroprotective agent and could regulate neuroinflammation. The present study intended to investigate whether treatment of minocycline maintain better cognition and mood function in a rat model of GWI and the potential mechanism. Methods Rats received 28 days of GWI-related chemical exposure and restraint stress, along with daily minocycline or vehicle treatment. Cognitive and mood function, neuroinflammation, neurogenesis and gut microbiota were detected. Results We found that minocycline treatment induced better cognitive and mood function in a GWI rat model, as indicated by open-field test, elevated plus maze test, novel object recognition test and forced swim test. Moreover, minocycline treatment reversed the altered gut microbiome, neuroinflammation and the decreased hippocampal neurogenesis of rats with GWI. Conclusion Taken together, our study indicated that minocycline treatment exerts better cognitive and mood function in GWI rat model, which is possible related to gut microbiota remodeling, restrained inflammation and enhanced hippocampal neurogenesis. These results may establish minocycline a potential prophylactic or therapeutic agent for the treatment of GWI.

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

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16193751 ◽

2019 ◽

Vol 16 (19) ◽

pp. 3751 ◽

Cited By ~ 9

Author(s):

Janulewicz ◽

Seth ◽

Carlson ◽

Ajama ◽

Quinn ◽

...

Keyword(s):

Gut Microbiome ◽

Gastrointestinal Symptoms ◽

Gulf War ◽

Gulf War Illness ◽

War Veterans ◽

Gulf War Veterans ◽

Gi Symptoms ◽

The Central Nervous System ◽

Stool Samples ◽

Sleep Difficulties

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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