Gulf War Illness and Gut Microbiome Dysbiosis: Treatment with Probiotics and Microbiota Transfer Therapy
[Technical Report, Annual Report]
Department of Psychiatry and Behavioral Neurosciences
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The purpose of this project is to test the hypothesis that Gulf War Illness GWI is mediated by a pathological alteration in the gut microbiome i.e., dysbiosis. It is known that the three primary symptom clusters of GWI gastrointestinal alterations, central nervous system dysfunction, and chronic fatigue can each be caused individually by an altered gut microbiome. Therefore, there is a strong likelihood that broad dysbiosis can contribute to the main symptoms of GWI in a concerted fashion. The primary scope of the project is to use a validated animal model of GWI and determine if this treatment results in a significant gut dysbiosis. Once this step is completed, the project will use probiotics and fecal microbiota transfer to re-balance the GWI-altered gut microbiome and, in turn, provide symptom relief. We treated mice with toxicants to which military personnel deployed to the Gulf were exposed e.g., pyridostigmine bromide PB plus permethrin PER. Thereafter, mice were maintained on a normal diet or one containing high fat. The high fat diet was included because a significant number of Veterans with GWI are overweightobese. We found that the taxonomic structure of the gut microbiome was significantly altered by the GWI agents. The high fat diet led to significant weight increases and this interacted with PB PER to worsen the dysbiosis. When mice on the high fat diet were returned to a normal diet, they lost weight and the alterations in the gut microbiome were corrected. We also found that mice treated with PB PER developed anxiety- and depression-like behaviors. These results confirm that GWI can be associated with a significant alteration in the gut microbiome, reflected as an increase in heterogeneity and altered community composition.
- Medicine and Medical Research