Gulf War Illness (GWI) affects an estimated 25-32% of the over 700,000 coalition troops deployed to the Persian Gulf as part of the First Gulf War. GWI causes a range of pain, fatigue, gastrointestinal, skin, neurologic, and respiratory symptoms. New treatments to reduce GWI-associated morbidity are critically needed. Research suggests a role for the gastrointestinal microbiome in mediating health, including through impacting metabolism and immunity. The disruption of this microbiome plays a role in multiple diseases, and preliminary data suggest that Veterans with GWI have altered gut microbiota. The investigators will evaluate the effectiveness of a dietary fiber prebiotic supplement intervention on improving the quality of life of Veterans with GWI.

Background: Despite medical advancements, Gulf War illness (GWI) treatment remains a major challenge. Gulf war veterans with GWI can experience acute or chronic disorders of diarrhea, nausea, joint pain, muscle pain, general fatigue, sleep problems skin rashes, wheezing, persistent cough, dizziness and headaches. It is estimated 25-32% of the over 700,000 coalition troops deployed report symptoms consistent with GWI, 47% of whom experience gut-related symptoms. Longitudinal studies have shown little to no overall improvement in symptoms over time. Currently there are very limited treatment courses for GWI and even fewer for gut-related symptoms leading to the advisory committee on GWIs call for research leading to effective treatments improving the health of GWVs. Studies have shown that the gut is comprised of diverse bacteria that plays a critical role in the health of an individual. Comprised gut microbiota can lead to serious consequences such as GWI. There is thus a critical need to identify a new treatment that is safe, effective with minimal adverse effect to reduce GWI-associated morbidity. Prebiotics are such an example. Prebiotics are natural fibers derived from carbohydrates and can be beneficial to gut microbiota (good bacterial in the gut). Resistant starches (RS) are dietary fiber prebiotics found naturally in many foods including potatoes, plantains, and legumes. In addition to being highly accessible, RS have been shown to be well tolerated with few adverse reactions. While no studies of RS exist in GWI patients, a meta-analysis of RS in IBD has shown RS to be an effective treatment in both animal and clinical studies where improvements in clinical remission and reduced mucosal damage were found. Furthermore, numerous studies have found RS to reduce inflammation in murine models of colonic inflammation and to modify the intestinal microbiota and associated metabolome in mice and swine.

Objectives: The investigators hypothesize those randomized to the RS prebiotic group will experience a reduction in GWI symptoms following the completion of the trial. The investigators also hypothesize the prebiotic group will have increased concentrations of SCFAs and SCFA-producing bacteria in the gut compared to those in the control group.

Methods: This is a phase II randomized clinical trial in Veterans with GWI experiencing gut symptoms. Subjects will be randomized to either taking a RS prebiotic daily for 4 weeks or to the control group (maintenance of normal diet). Subjects will provide stool and serum samples as well as complete a series of health history and dietary questionnaires.

Inclusion Criteria:

1. Ability to provide informed written consent

2. Willing to comply with all study procedures and be available for the duration of the study (including providing stool samples)

3. Meeting the modified Kansas GWI case definition* with gut symptoms endorsed

4. Deployed to Persian Gulf during Operations Desert Storm or Desert Shield56.Aged 50-85 years old

   • Moderate to severe GWI symptoms lasting at least 6 months in a minimum of three of the six symptom domains (one of which must be fatigue). The symptom domains are:

     • Pain (joint pain, muscle pain)
     • Gastrointestinal (diarrhea, nausea, vomiting, cramping)
     • Respiratory (persistent cough, wheezing)
     • Skin (rashes)
     • Fatigue (sleep problems, fatigue)
     • Neurologic (memory problems, headaches, dizziness, mood changes)

Exclusion Criteria:

1. A Known SARS-CoV-2 infection in the last 60 days and/or with a diagnosis of post-acute sequelae of COVID-19 (PASC, sometimes called long COVID) defined as COVID-19 symptoms lasting for greater than 6 months.
2. Subjects identified as, or appearing to, lack consent capacity
3. Alcohol abuse (greater than 14 drinks per week for men and 7 drinks per week for women)
4. Use of investigational drugs, biologics, or devices within 30 days prior to randomization.
5. Individuals who are pregnant, lactating or planning on becoming pregnant during the study.
6. Diagnosed inflammatory bowel disease, Crohn's disease, or Celiac's disease
7. Uncontrolled/untreated hypothyroidism
8. Previous gastrointestinal surgery (colorectal surgery, gastric bypass, intestinal resection)
9. Systemic antibiotics in the last 30 days
10. Fecal microbiota transplant in the last 30 days
11. Active dysphagia
12. Allergies to any of the ingredients in MSPrebiotic
13. Use of immunomodulatory medications in the last 30 days
14. Any other factor, condition, or medication not listed above the Investigators believe will affect the response in the gut or the interpretation of results.

A BioProject will be created with NCBI and sequencing data will be shared there with a limited, deidentified set of metadata from participants. Additional data can be obtained from the research team with permissions.

3 years

Written requests for access to the data will be accepted. Data and documentation will be available under a data use agreement (DUA) that provides a commitment to use data for research purposes only, not to attempt to identify participants, to secure data using appropriate computer technology, and to destroy/return data after analyses are complete.