Prolonged treadmill running in normobaric hypoxia causes gastrointestinal barrier permeability and elevates circulating levels of pro- and anti-inflammatory cytokines

Garrett W Hill, Trevor L Gillum, Ben J Lee, Phebe A Romano, Zach J Schall, Ally M Hamilton, Matthew R Kuennen

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


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 IO 2) = 20.9%) and the other in normobaric hypoxia (HYP: F IO 2 = 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 (SpO 2) was measured with pulse oximetry. Absolute tissue saturation (StO 2) 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, 1hof 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%), SpO 2 (–16%), and StO 2 (–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%, respec-tively) 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.

Original languageEnglish
Pages (from-to)376-386
Number of pages11
JournalApplied Physiology, Nutrition, and Metabolism
Issue number4
Early online date10 Sep 2019
Publication statusPublished - Apr 2020
Externally publishedYes


  • Altitude training
  • Cardiopulmonary response
  • Endurance exercise
  • Exercise immunology
  • Gastrointestinal barrier
  • Inflammation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Nutrition and Dietetics
  • Physiology (medical)


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