Characterising the gut microbiome in veterans with Gulf War Illness
by Dr. Julie A. Keating
Based on estimates by the Gulf War Research Advisory Committee and the 2010 Institute of Medicine report, approximately 25%–35% of the 1991 Gulf War Veteran population report symptoms consistent with Gulf War Illness (GWI).1–3 GWI is a chronic, multi-symptom illness characterised by fatigue, pain, irritable bowel syndrome and problems with cognitive function. GWI is a disabling problem for many Gulf War Veterans, and there have been only modest advances in the treatment for GWI. There remains a critical need for identification of innovative, novel therapies.4
Gut microbiota perturbation plays a key role in the symptomatology of chronic multi-symptom illnesses similar to GWI, such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).5–7 Although GWI and ME/CFS are considered distinct conditions, both of them are characterised by similar complex, multi-organ chronic signs and symptoms. Moreover, Gulf War Veterans are more likely to meet the case definition for ME/CFS than non-deployed era Veterans.8 Given the overlap and similarity of symptoms, it is possible that gut microbiota abnormalities as described in ME/CFS may also be responsible for the symptomatology in GWI.9 10
Data suggest that individuals with GWI have an increased prevalence of gastrointestinal symptoms such as diarrhoea and abdominal pain and cramps,11 which may result in or be caused by intestinal dysbiosis (ie, alteration in the microbial community), low grade inflammation and immune activation.12 Given the body’s largest immune reservoir resides in the gastrointestinal tract, interventions such as probiotics, dietary interventions or faecal microbiome transplants could favourably alter the gut microbiome, improve mucosal barrier function and decrease proinflammatory cytokines. Overall, interventions targeting the gut microbiome have the potential to positively influence not only gastrointestinal symptoms but also non-gastrointestinal symptoms in GWI Veterans. However, an understanding of the structure and function of the gut microbiome in Veterans with GWI is essential to the development of such interventions. Based on our review of the literature, the gut microbiome in Veterans with GWI and its relationship to the symptomatology of GWI have not yet been reported.
Here, we are characterising the gut microbiome of Gulf War Veterans with GWI compared with healthy Gulf War Veterans without GWI. This work is ongoing (2018–2020) and will be among the first to examine gut microbiome in Gulf War Veterans and will advance our understanding of the pathophysiology of GWI.
GWI is a disabling problem for many Gulf War Veterans. To date, there has been little information on the pathology of the disease. There are no scientifically validated, effective treatments for GWI, though there have been modest advances in GWI treatments.4 Thus, the need for innovative treatment strategies remains critical. The gut microbiome presents a novel target for investigation. The high prevalence of gastrointestinal dysfunction in Gulf War Veterans in the context of literature demonstrating intestinal dysbiosis in patients with ME/CFS, another complex condition, suggests that alterations in the gut bacteria could play a role in the pathophysiology of GWI. This study is among the first to examine the gut microbiome structure and function in Gulf War Veterans.
The brain–gut axis—biochemical signalling between the gastrointestinal tract and the central nervous system—is increasingly recognised as important to health.34–40 The gut microbiome is known to impact the production, expression and turnover of neurotransmitters such as serotonin. These neurotransmitters affect cognitive and functional nervous system processes such as behaviour, mood and fatigue. The microbiome also affects the intestinal barrier and tight junction integrity, and bacterial metabolites influence mucosal immune regulation. Previous studies have shown chemical exposures common to the Gulf War (eg, the anti-nerve agent pyridostigmine bromide) can be used to create a mouse model of GWI.15 41 42 These mouse models of GWI show an altered gut microbiome and a connection between this altered microbiome and neuroinflammation, suggesting a role for the brain–gut axis in GWI.15 42 Through analyses of inflammatory markers as well as the structure and function of the microbiome in Veterans with GWI, our study aims to improve our understanding of the brain–gut axis and the role of the microbiome in GWI in humans.
Preliminary data from studies in mice and humans with ME/CFS have found a potential benefit in the use of probiotics to ameliorate fatigue symptoms.43–46 Initial studies have also found improvement in ME/CFS symptoms through the use of faecal microbiota transplant47; additional studies are ongoing into the use of faecal microbiota transplant to treat ME/CFS symptoms.
If we find that the gut microbiome is altered in Veterans with GWI, then probiotics, dietary intervention or faecal microbiota transplant may represent low-cost, low-risk treatment options for GWI symptoms. At the conclusion of this study, we expect to be positioned to pursue a clinical trial to investigate interventions targeting the gut microbiome as a way to alleviate symptoms in Veterans with GWI.