Gulf War Illness Susceptibility and Gut Microbiome Dysbiosis: A Search for Biomarkers to Boost Resilience
Abstract
Overarching Challenges: Using an established mouse model of Gulf War Illness (GWI) and standard diagnosis criteria, this research project will address the following FY20 GWIRP challenges: 1) Subtyping: identification of gut microbiome dysbiosis as an underlying pathobiological factor contributing to the differences between the subpopulation of individuals that are susceptible to develop GWI and the ones who show resilience; 2) Diagnosis: identification of signature elements in the gut microbiome that would function as biomarkers for susceptibility or that would confer resilience; and 3) Treatment: identification of therapeutic approaches aiming to restore gut microbiome homeostasis and rebalance its metabolites to reduce disease vulnerability and attenuate symptom severity. Objective and Rationale: The main objective of this project is to evaluate the composition of the gut microbiome and its bacterial metabolites in GWI-susceptible and GWI-resilient mice to establish biomarkers underlying each condition. In addition, two therapeutic approaches will be tested for their ability to re-balance the gut microbiome perturbations and attenuate symptom severity in GWI-susceptible subjects. These include the readily available fecal microbiota transplantation (FMT) and butyrate supplementation. Our rationale is based on the fact that 25%-35% of Gulf War Veterans become sick while all the deployed Service Members of this conflict were exposed to similar conditions. Besides the evidence of gut microbiota alterations in Veterans diagnosed with GWI and in animal models of this illness, every hallmark of the multi-symptom GWI falls under the regulation of the gut microbiome. Lastly, it has been proven that restitution of the gut microbiome balance in conditions prevalent in GWI can mitigate symptom severity. Applicability: This research project will lead to a better understanding of the mechanistic underpinnings of GWI and the factors contributing to differential susceptibility to this complex disorder by addressing the following: 1) determination of specific gut microbiome elements associated with either vulnerability or resilience to GWI; 2) identification of signature changes in the gut microbiota and bacterial metabolites that could serve as biomarkers for specific symptom clusters and enhance diagnosis; 3) design of more adequately focused treatments that would mitigate symptom severity, promote resilience, or even prevent the onset of the disorder through the use of FMT and functionally versatile compounds such as butyrate. FMT is a safe, well-tolerated approach for humans that is becoming an accepted therapy for Veterans with serious gastrointestinal conditions, and butyrate is a dietary element with no posed threat to health; 4) considerable potential to translate these therapeutic approaches to benefit Veterans of other conflicts that are afflicted with similar chronic multi-symptom disorders. It is now recognized that although Veterans from the Gulf War tend to be sicker, their health conditions are not exclusive to that cohort, as similar complex conditions are also observed in Veterans and Service Members from more recent combat operations (e.g., Iraq, Afghanistan).
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110553
Entities
People
- Mariana Angoa-pérez
Organizations
- United States Army
- Wayne State University