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

PURPOSE: This study examined the impact of treadmill running in normobaric hypoxia on gastrointestinal
barrier permeability and the systemic inflammatory response.

METHODS: Ten recreationally-active participants
completed two 1h bouts of matched-workload treadmill exercise(65% normoxic VO2max) in counterbalanced
order. One bout was performed in normoxia(NORM: FIO2=20.9%) and the other in normobaric hypoxia(HYP:
FIO2=13.5%). Minute ventilation(VE), respiratory rate(RR), tidal volume(VT), oxygen consumption(VO2), carbon
dioxide production(VCO2), respiratory quotient(RQ), 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(IL-1Ra, IL-6, IL-10, TNFα) were assayed from plasma samples collected Pre, Post, 1h-Post, and
4h-Post exercise. Data were analyzed with 2-Way(Condition*Time) RM ANOVAs and Newman-Keuls post hocs
were run where appropriate(p<0.05).

RESULTS: As compared to NORM, 1h of treadmill exercise in HYP caused
greater(p<0.05) changes in VE(+30%), RR(+16%), VT(+10%), VCO2(+18%), RQ(+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 Post(+68%) and IL-1Ra at 1h-Post(+266%). IFABP and IL-1Ra did not change following NORM exercise. IL-6 and IL-10 increased with exercise in both
study conditions but were increased more(p<0.05) following HYP exercise at Post(+705% and +127%;
respectively) and 1h-Post(+400% and +128%; respectively).

KEY FINDINGS:
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.