This study examined the impact of treadmill running in normobaric hypoxia on gastrointestinal barrier permeability and the systemic inflammatory response. Ten recreationally active participants completed two 1-h bouts of matched-workload treadmill exercise (65% normoxic maximal oxygen consumption) in counterbalanced order. One bout was performed in normoxia (NORM: fraction of inspired oxygen (F_IO₂) = 20.9%) and the other in normobaric hypoxia (HYP: F_IO₂ = 13.5%). Minute ventilation, respiratory rate (R_R), tidal volume (V_T), oxygen consumption, carbon dioxide production, respiratory exchange ratio (RER), and heart rate (HR) were measured with a metabolic cart. Peripheral oxygen saturation (SpO₂) was measured with pulse oximetry. Absolute tissue saturation (StO₂) was measured with near-infrared spectroscopy. Fatty acid-binding protein (I-FABP) and circulating cytokine concentrations (interleukin (IL)-1Ra, IL-6, IL-10) were assayed from plasma samples that were collected pre-exercise, postexercise, 1 h-postexercise, and 4 h-postexercise. Data were analyzed with 2-way (condition × time) repeated-measures ANOVAs. Newman-Keuls post hoc tests were run where appropriate (p < 0.05). As compared with NORM, 1 h of treadmill exercise in HYP caused greater (p < 0.05) changes in minute ventilation (+30%), R_R (+16%), V_T (+10%), carbon dioxide production (+18%), RER (+16%), HR (+4%), SpO₂ (-16%), and StO₂ (-10%). Gut barrier permeability and circulating cytokine concentrations were also greater (p < 0.05) following HYP exercise, where I-FABP was shown increased at postexercise (+68%) and IL-1Ra at 1 h-postexercise (+266%). I-FABP and IL-1Ra did not change (p > 0.05) following NORM exercise. IL-6 and IL-10 increased with exercise in both study conditions but were increased more (p < 0.05) following HYP at postexercise (+705% and +127%, respectively) and 1 h-postexercise (+400% and +128%, respectively). Novelty Normobaric hypoxia caused significant desaturation and increased most cardiopulmonary responses by 10%-30%. Significant gut barrier permeability and increased pro- and anti-inflammatory cytokine concentrations could promote an "open window" in the hours following HYP exercise.

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