# Humanized Mouse Model of Gulf War Veterans' Illness

> **NIH VA I21** · JOHN D DINGELL VA MEDICAL CENTER · 2024 · —

## Abstract

Gulf War Veterans' Illnesses (GWVI) is a complex constellation of symptoms that have persisted in Gulf War
Veterans (GWV) more than 25 years after their deployment to the Gulf. These symptoms are so diverse, they
baffle diagnostic criteria. As a result, consideration of GWVI as a bona fide illness has progressed slowly from
denial of its existence to the use of such terms as “unexplained illnesses” (used by the VA) and “multisymptom
illness”. The Institute of Medicine Committee on Gulf War and Health (2016) concludes that GWVI is not a
psychosomatic condition and sufficient evidence now exists to conclude that a causal relationship exists
between being deployed to the Gulf War and the health outcomes associated with this disorder. This
Committee noted that little progress has been made in elucidating the pathological mechanisms that underlie
the complex symptoms associated with GWVI and as a result, “it does not appear that a single mechanism can
explain the multitude of symptoms seen in Gulf War Illness, and it is unlikely that a single definitive causal
agent will be identified this many years after the war” (p. 3 of report). Another complexity relating to GWVI is
establishing the toxicant exposure conditions to which GWVs were exposed. Potential agents include depleted
uranium, pyridostigmine bromide (PB), sarin, vaccines, permethrin (PER) and other insecticide repellents,
fuels, infectious diseases, stressors, burn pits and blast exposure. These potential toxicants form the basis for
numerous animal models of GWVI. It is interesting that 3 of the major symptoms of GWVI- GI disruptions,
PTSD/anxiety and chronic fatigue- can be caused individually by a dysbiosis in the gut microbiome, so it is
reasonable to hypothesize that imbalances in the gut microbiome might contribute to these major 3 symptoms
of GWVI collectively, and others as well. We (and others) have shown recently that PER/PB results in a
significant alteration in the diversity and composition of the gut microbiome. Our animal model studies of
GWVI-gut microbiome interactions are supported by a BLR&D Merit Award. A significant gap in the
understanding of the pathophysiological underpinnings of GWVI arises from the lack of knowledge of the exact
toxicant exposures. Self-reporting by GWVs is the basis of what is known about exposures, so it is hard to
state with certainty, which agents (single, combinations) and their doses, frequencies and durations led to
GWVI. This is an important point because we are learning that outcomes from animal model studies are
dependent on the specific agent(s) used. One approach that could remove toxicant exposure conditions from
the GWVI equation is the development of a humanized mouse model. In this manner, the GWVs toxicant
exposures are already incorporated into the disorder along with its chronic, persistent symptomology. The
objective of this Pilot Project is to develop a humanized mouse model via fecal microbiota transplantation
(FMT) from stool sa...

## Key facts

- **NIH application ID:** 10767127
- **Project number:** 5I21BX005850-02
- **Recipient organization:** JOHN D DINGELL VA MEDICAL CENTER
- **Principal Investigator:** Mariana Angoa-Perez
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10767127

## Citation

> US National Institutes of Health, RePORTER application 10767127, Humanized Mouse Model of Gulf War Veterans' Illness (5I21BX005850-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10767127. Licensed CC0.

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