Exercise in hypobaric hypoxia increases markers of intestinal injury and symptoms of gastrointestinal distress

Abstract

New Findings What is the central question of this study?What is the effect of hypobaric hypoxia on markers of exercise‐induced intestinal injury and symptoms of gastrointestinal (GI) distress? What is the main finding and its importance?Exercise performed at 4300 m of simulated altitude increased intestinal fatty acid binding protein (I‐FABP), claudin‐3 (CLDN‐3) and lipopolysaccharide binding protein (LBP), which together suggest that exercise‐induced intestinal injury may be aggravated by concurrent hypoxic exposure. Increases in I‐FABP, LBP and CLDN‐3 were correlated to exercise‐induced GI symptoms, providing some evidence of a link between intestinal barrier injury and symptoms of GI distress. Abstract We sought to determine the effect of exercise in hypobaric hypoxia on markers of intestinal injury and gastrointestinal (GI) symptoms. Using a randomized and counterbalanced design, nine males completed two experimental trials: one at local altitude of 1585 m (NORM) and one at 4300 m of simulated hypobaric hypoxia (HYP). Participants performed 60 min of cycling at a workload that elicited 65% of their NORM trueV̇normalO2max${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$. GI symptoms were assessed before and every 15 min during exercise. Pre‐ and post‐exercise blood samples were assessed for intestinal fatty acid binding protein (I‐FABP), claudin‐3 (CLDN‐3) and lipopolysaccharide binding protein (LBP). All participants reported at least one GI symptom in HYP compared to just one participant in NORM. I‐FABP significantly increased from pre‐ to post‐exercise in HYP (708 ± 191 to 1215 ± 518 pg ml−1; P = 0.011, d = 1.10) but not NORM (759 ± 224 to 828 ± 288 pg ml−1; P > 0.99, d = 0.27). CLDN‐3 significantly increased from pre‐ to post‐exercise in HYP (13.8 ± 0.9 to 15.3 ± 1.2 ng ml−1; P = 0.003, d = 1.19) but not NORM (13.7 ± 1.8 to 14.2 ± 1.6 ng ml−1; P = 0.435, d = 0.45). LBP significantly increased from pre‐ to post‐exercise in HYP (10.8 ± 1.2 to 13.9 ± 2.8 μg ml−1; P = 0.006, d = 1.12) but not NORM (11.3 ± 1.1 to 11.7 ± 0.9 μg ml−1; P > 0.99, d = 0.32). I‐FABP (d = 0.85), CLDN‐3 (d = 0.95) and LBP (d = 0.69) were all significantly higher post‐exercise in HYP compared to NORM (P ≤ 0.05). Overall GI discomfort was significantly correlated to ΔI‐FABP (r = 0.71), ΔCLDN‐3 (r = 0.70) and ΔLBP (r = 0.86). These data indicate that cycling exercise performed in hypobaric hypoxia can cause intestinal injury, which might cause some commonly reported GI symptoms.

Ibuprofen Increases Markers of Intestinal Barrier Injury But Suppresses Inflammation at Rest and After Exercise in Hypoxia

“…Furthermore, our findings of increased MCP-1, TNF-α, IL-1β, and IL-10 expand upon our previous work and confirm the work of Hill et al (36), who demonstrated that exercise in hypoxia increases the circulation of both proinflammatory and anti-inflammatory cytokines. However, in contrast to our previous study (8), the present findings show that exercise in hypoxia alone (i.e., placebo trial) was not sufficient to increase LBP. This was somewhat surprising given the large effect size ( d = 1.12) that we previously reported, although this discrepancy is likely explained by differences in exercise intensity (8).…”

“…As expected, exercise in hypoxia increased markers of intestinal cell injury, intestinal permeability, microbial translocation, and inflammation, which partly confirm and build upon our previous findings (8). Indeed, here we report that exercise at simulated 4300 m caused intestinal injury, as noted by the preexercise to postexercise increases in I-FABP and I-BABP.…”

“…The greater ΔI-FABP and L/R ratio in the ibuprofen trial suggests that ibuprofen aggravated intestinal injury and intestinal permeability induced by exercise in hypoxia. It has been previously shown that exercise in hypoxia increases markers of intestinal barrier injury and microbial translocation (8,36,38); however, we are the first to show that ibuprofen worsens these effects. Furthermore, although ΔI-BABP, ΔLBP, and ΔsCD14 were similar between trials, these markers were all significantly higher after exercise in the ibuprofen trial, an outcome likely linked to higher basal levels of these markers.…”

“…Recent data from our laboratory have shown that exercise in hypoxia can elevate circulating markers of enterocyte damage and intestinal barrier injury (8). Given the known effects of NSAIDs on the gut, we hypothesized that ibuprofen would aggravate intestinal barrier dysfunction induced by exercise in hypoxia and further contribute to high-altitude associated GI complaints.…”

“…However, it has been speculated that ibuprofen may worsen symptoms of gastrointestinal (GI) distress or even increase the risk of GI bleeding (5). This is of particular concern for those traveling to high-altitude because GI distress and GI bleeding have been observed during hypoxic exposures in the absence of ibuprofen (6)(7)(8)(9). Furthermore, ibuprofen is commonly used by athletes and military personnel to treat musculoskeletal injuries and reduce acute pain and thus may be problematic for individuals exercising or performing physical work at altitude (10,11).…”