The aim of this randomized, crossover clinical trial is to determine the efficacy of a gut microbiota-targeted nutritional intervention containing a blend of fermentable fibers and polyphenols (FP) for mitigating increases in GI permeability, and decrements in immune function and neuropsychologic performance following rapid ascent to simulated high altitude. Fifteen healthy young adults will participate in each of three study phases that include a 14-day supplementation period in which participants will consume 1 of 2 supplement bars: placebo (PL, will be consumed during 2 phases) and FP supplementation (will be consumed during one phase only). During the final 2-d of each phase, participants will live in a hypobaric chamber under sea level or high altitude conditions.

The collection of microbes inhabiting the human gastrointestinal (GI) tract, known as the gut microbiota, is increasingly recognized as a mediator of GI, immunologic, and neuropsychologic responses to various environmental and physiologic stressors. The hypobaric hypoxia characteristic of high altitude environments is a stressor that has recently been associated with increased GI permeability, and which has been shown to cause decrements in immune, neuropsychological and physical function. To what extent modulation of the human gut microbiota can mitigate these responses during high altitude exposure is undetermined. The aim of this randomized, crossover clinical trial is to determine the efficacy of a gut microbiota-targeted nutritional intervention containing a blend of fermentable fibers and polyphenols (FP) for mitigating increases in GI permeability, and decrements in immune function and neuropsychologic performance following rapid ascent to simulated high altitude. Fifteen healthy young adults will participate in each of three study phases in random order. Each phase will include a 14-day supplementation period in which participants will consume 1 of 2 supplement bars: placebo (PL, will be consumed during 2 phases) and FP supplementation (will be consumed during one phase only). During the final 2-d of each phase, participants will live in a hypobaric chamber. During one phase the chamber environment will mimic low-altitude conditions (SHAM). During two phases the chamber environment will mimic the barometric pressure at Pike's Peak CO (460 mmHg; HA).

Inclusion criteria:

• Men and women aged 18 - 39 years (active duty personnel who are 17 yr of age will also be allowed to participate)
• In good health
• Physically active
• For active duty, passed most recent body composition assessment; for civilians, body mass index (BMI) ≤ 30.0 kg/m2.
• Self-reports having a bowel movement at least as frequently as every-other-day
• Self-reports normal vision (with or without glasses) and hearing

Exclusion Criteria:

• Born at altitudes greater than 2,100 m (~7,000 feet)

• Living in areas that are more than 1,200 m (~4,000 feet), or have traveled to areas that are more than 1,200 m for five days or more within the last 2 mo

• Pregnant, expecting to become pregnant during study, or breastfeeding

• Any of the following medical conditions:

  1. Musculoskeletal injuries that compromise exercise capability
  2. Metabolic or cardiovascular abnormalities (e.g., kidney disease, diabetes, cardiovascular disease, etc.)
  3. Suspected or known strictures, fistulas, or physiological/mechanical GI obstruction
  4. Evidence of apnea or other sleeping disorders
  5. Evidence of prior high altitude pulmonary or cerebral edema diagnosis
  6. Disease of the GI tract including, but not limited to diverticulitis, inflammatory bowel disease, peptic ulcer disease, Crohn's disease, ulcerative colitis
  7. Anemia or Sickle Cell Anemia/Trait
  8. Alcoholism or other substance abuse issues
  9. History of gastric bezoar
  10. Swallowing disorders; severe dysphagia to food or pills
  11. Implanted or portable electro-mechanical medical devices
  12. Allergy to skin adhesive

• Past GI surgery

• Colonoscopy within 3 months of study participation

• Taking prescription medications other than a contraceptive (unless approved by Medical Office and study PI)

• Regular use of over-the-counter medications (including antacids, laxatives, stool softeners, and anti-diarrheals) unless approved by Medical Office and study PI

• Any use of antibiotics, except topical antibiotics, within 3 months of study participation

• Not willing to refrain from using non-steroidal anti-inflammatory medications (NSAIDs) or antihistamine during the study

• Not willing to stop consumption of prebiotic- or probiotic-containing supplements (e.g.,VSL#3, PRO-15, etc.), or other dietary supplements at least 2 weeks before and throughout study participation

• Not willing to stop consumption of probiotic-containing foods (e.g., yogurt, etc.) during study participation.

• Not willing to refrain from smoking any nicotine product (includes e-cigarettes), vaping, and chewing tobacco during controlled-diet periods.

• Not willing to abstain from caffeine and alcohol during controlled-diet periods.

• Allergies, intolerances, unwillingness or inability to eat provided foods and beverages

• Following vegetarian/vegan diet

• Unable to regularly sleep for 7-10 hr/night

• Any previous blood donation, within 8 weeks of the first blood draw of the study, of a volume that when combined with the amount of blood to be collected during the study would exceed 550 mL

Double-blinded