The primary objective of this clinical trial is to determine if treatment with Butyrate formulation that consists of butyric acid as calcium and magnesium derivatives (Ca-Mg Butyrate) improves the physical function of men and women Veterans suffering from Gulf War Illness (GWI). The primary outcome measure is a change from baseline on the Short Form Health Survey 36-item (VSF-36), with respect to physical functioning and symptoms. The secondary outcome will focus on the drug's role in (a) restoring gut microbiome and virome, (b) decreasing gastrointestinal disturbances (constipation, diarrhea, pain), (c) decreasing chronic fatigue, (d) decreasing systemic inflammation, and (e) a decrease in cognitive deficits.

Nearly one third of 700,000 military personnel deployed during Desert Shield and Desert Storm (Aug 2, 1990 to July 31, 1991) in the Kuwaiti War Theater are suffering from Gulf War Illness (GWI), an unexplained chronic illness characterized by multiple symptoms. The illness has taken a heavy toll on deployed Veterans' overall quality of life. Recent research has revealed the host gut microbiome's role in gastrointestinal disturbance, systemic inflammation, and neurotrophic abnormalities in Gulf War Illness mouse models. Also, short-chain fatty acids such as butyrate restored a healthy microbiome and improved gut microbial metabolism apart from attenuating GWI symptom persistence in preclinical studies. Butyrate, a nutraceutical endogenously produced in the host gut following bacterial fermentation, has shown promise in gastrointestinal disturbances such as irritable bowel syndrome (IBS) and Inflammatory bowel disease (IBD).

This is a randomized, two-group, double-blind, placebo-controlled, Phase II clinical trial. The treatment group will receive microencapsulated butyrate capsules (600 mg twice a day for 18 weeks). The placebo group will receive a matching placebo formulation twice a day for 18 weeks. However, after two weeks of the treatment (20 weeks) there will be a follow up virtual visits. The primary outcome measure for this clinical trial is a change from baseline of VSF-36 and CVLT III test scores with respect to physical and mental functioning and symptoms. The secondary outcome measures include changes from baseline of host-microbiome signature, intestinal permeability assessment, peripheral pro-inflammatory biomarkers, and GWI-associated symptoms IBS, chronic pain, fatigue, sleep issues, and cognitive impairment.

Inclusion Criteria:

• Gulf war era veteran deployed 40 and 70 years old, in good health by medical history prior to 1990 meeting GWI case definition of CDC and Kansas criteria and
• currently have no exclusionary diagnoses (self- reported) that could reasonably explain the symptoms of their fatiguing illness. The severity of illness is moderate to severe, scoring less than 30 of 100 on the physical domain of VSF36 .

Exclusion Criteria:

• Untreated schizophrenia,
• Untreated bipolar disorder,
• Untreated delusional disorders,
• Untreated dementias of any type and
• active alcoholism or drug abuse.
• Medical conditions excluded include (i) organ failure, (ii) defined rheumatologic inflammatory disorders, and (iii) transplant.
• Use of Butyrate in any form in the 3 months prior to study drug, medications that would impact gut motility, diarrhea, chronic pain, and immune function e.g., steroids, (Last 3 months)
• immunosuppressive drugs or biologic response modifiers within 3 months of study entry will be used as exclusion criteria.
• Pregnancy, or planned pregnancy in the next 6 months,
• Body mass index more than 35
• Specific diets that may have enhanced or enriched fiber or butyrogenic formulations (FODMAP)
• Medications that could potentially impact immune function in the past one month will be excluded (e.g., steroids, antibiotics, immunosuppressives;
• Medications containing supplement calcium or magnesium butyrate should not be taken for at least 3 months before study entry.
• Nutraceuticals that are formulated to impact gut microbiome or immune health) and use of drugs that affect GI motility and use of any antibiotic in the last 2 months.
• Known allergy to butyrate supplements or their derivatives such as sodium salts or hydroxy derivatives of butyrate and/or inactive ingredients of active and placebo soft gelatin will also be excluded.
• Current evidence of celiac disease or late-stage cirrhosis of the liver, Giardia antigen presence, Clostridium difficile toxin in stool, tissue transglutaminase antibody, recent change in gastrointestinal medications, use of drugs that affects gastrointestinal motility, and use of any antibiotic in the last two months also will be excluded.

Quadruple, participants, care provider, investigators and outcome assessor will not have access to blinding. Only research pharmacist to distribute the drug or placebo and study coordinator to keep a confidential and secure records, will have access to the blinding.