# BCCMA: Targeting Gut-Microbiome in Veterans Deployment Related Gastrointestinal and Liver Diseases; CMA1- The Role of GWI Gut Microbiome in Susceptibility to Diarrheal Diseases

> **NIH VA I01** · JESSE BROWN VA MEDICAL CENTER · 2023 · —

## Abstract

This revised BLRD and CSRD Collaborative Merit Award (BCCMA) application is being submitted as part of a
group of 5-linked CMAs from nationwide VA investigators in gastrointestinal (GI) and liver diseases, who formed
a national steering committee after participating in a successful field-based meeting in San Diego in May 2019
(funded by VAORD). The roadmap developed at this meeting was published in the journal “Gastroenterology”
(PMC7249241). This cluster of CMAs is aimed at in depth understanding of the emerging role of gut microbiome
in the pathophysiology of Veterans deployment related GI and liver diseases including the Gulf War Illness (GWI),
Post Traumatic Stress Disorder (PTSD) and Inflammatory Bowel Diseases (IBD), and to develop potential
biotherapeutics to alleviate the disease symptoms. This specific proposal CMA1, is driven by the facts that
while diarrheal disorders are highly prevalent in Veterans with GWI and are a major cause of high morbidity,
the pathophysiology of GWI is not well-defined, and the treatment options are inadequate. Therefore, in
view of the emerging role of the gut microbiome in GWI, there is a critical need to better understand the
role of microbial dysbiosis and the mechanisms involved in higher incidence of diarrheal disorders and IBS
in these Veterans. Recent studies have further highlighted the crucial role of gut microbiome in
susceptibility to diarrheal pathogens. For example, gut microbiome has been shown to be the key determinant
in susceptibility to infection and diarrhea by C. rodentium (CR, murine counterpart of the human
enteropathogenic E. coli). Additionally, fecal microbial transplant (FMT) based treatment strategies for C. difficile
infection further support the critical role of gut microbiome in diarrheal diseases. However, direct causal
relationship of microbial dysbiosis observed in GWI Veterans and diarrheal illnesses remains uninvestigated. In
this regard, in preliminary studies we established a humanized GWI mouse model where FMT from GWI
Veterans in mice for 14 days almost recapitulated some features of the functional bowel disorders associated
with GWI, including a) significant dysregulation in intestinal barrier integrity; and b) mild inflammation as
assessed by neutrophil infiltration. Another novel and striking finding in the humanized GWI mice was a marked
decrease in colonic expression of the key chloride transporter (DRA, Down Regulated in Adenoma). Of note,
decreased DRA expression is a key event in infectious or IBD associated diarrhea and is also linked to
compromised barrier integrity. Also, in preliminary studies, we observed that DRA KO mice were much more
susceptible to CR infection. Based on these data, we hypothesize that “Dysbiosis in GWI Veterans is
associated with compromised barrier integrity and decreased DRA expression which contributes to
increased predisposition of veterans to pathogen infections and diarrhea. We propose to utilize state-of-
the-art animal models e....

## Key facts

- **NIH application ID:** 10485710
- **Project number:** 1I01BX005862-01A1
- **Recipient organization:** JESSE BROWN VA MEDICAL CENTER
- **Principal Investigator:** Pradeep K Dudeja
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-10-01 → 2026-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10485710

## Citation

> US National Institutes of Health, RePORTER application 10485710, BCCMA: Targeting Gut-Microbiome in Veterans Deployment Related Gastrointestinal and Liver Diseases; CMA1- The Role of GWI Gut Microbiome in Susceptibility to Diarrheal Diseases (1I01BX005862-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10485710. Licensed CC0.

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