Gut microbiota-targeted dietary supplementation with fermentable fibers and polyphenols prevents hypobaric hypoxia-induced increases in intestinal permeability

Interactions between the gut microbiota and intestinal barrier may contribute to the pathophysiology of high-altitude illnesses. This study aimed to determine the effects of targeting the gut microbiota using dietary supplementation with a blend of fermentable fibers and polyphenol sources on gut microbiota composition, fecal short-chain fatty acids (SCFAs), and intestinal function and permeability during hypobaric hypoxia exposure. Healthy adults participated in a randomized, placebo-controlled, crossover study. Food products containing oligofructose-enriched inulin, galacto-oligosaccharide, high-amylose corn starch, cocoa, green tea and cranberry extracts, and blueberry powder (FP) or maltodextrin (placebo; PL) were consumed daily during three 2-wk phases separated by a ≥1-wk washout. During the final 36 h of each phase, participants resided in a hypobaric chamber simulating low (LA; 500 m) or high (HA; 4,300 m) altitude creating three experimental conditions: PL + LA, PL + HA, and FP + HA. Twenty-six participants completed ≥1 study phase and 13 [12 male; 21 ± 3 yr; body mass index (BMI) 25.4 ± 2.4 kg/m²] completed all three phases. Results demonstrated that FP mitigated hypoxia-induced increases in intestinal permeability within the small intestine and proximal colon while increasing <i>Bifidobacterium</i> relative abundance and decreasing gut microbiota α-diversity and colonic pH. Higher <i>Bifidobacterium</i> relative abundance and lower colonic pH were associated with greater reductions in intestinal permeability. However, FP did not alter fecal SCFA concentrations and increased gastrointestinal symptoms and altitude sickness during hypobaric hypoxia exposure. Findings suggest that targeting the gut microbiota with a combination of fermentable fibers and polyphenols can prevent hypobaric hypoxia-induced increases in intestinal permeability but that benefit does translate into a reduction in altitude illness symptoms.<b>NEW & NOTEWORTHY</b> Dietary supplementation targeting the gut microbiota may provide novel approaches to improving physiologic responses to environmental stressors such as those experienced during sojourn at high terrestrial altitudes. This study demonstrated that gut microbiota-targeted dietary supplementation using a blend of fermentable fibers and polyphenol sources can prevent hypobaric hypoxia-induced decrements in intestinal permeability. Findings support the emerging concept that the gut microbiota may be a modifiable factor influencing physiologic responses in austere environments.