Differential Intestinal Epithelial Injury Following Passive and Exertional Hyperthermia

Abstract Background Passive and exertional hyperthermia can compromise gastrointestinal (GI) integrity, contributing to systemic complications and heat stroke. Intestinal epithelial injury, a potential early event in this cascade, is likely multi-factorial and context-dependent, influenced by thermal, metabolic and mechanical stress. We compared the effects of passive hyperthermia (PaH) and exertional hyperthermia (RUN) at matched peak body core temperature (Tc) on intestinal epithelial injury and endotoxin translocation to delineate the relative contributions of these mechanisms. A prolonged brisk walking (WALK) condition was included as an exploratory condition relevant to occupational heat exposures. Methods In this randomised, counterbalanced, repeated-measures study conducted per CONSORT guidelines, 15 male endurance athletes (age: 26 ± 3 years, VO2peak: 64 ± 6 ml/kg/min) completed PaH, WALK and RUN. PaH involved warm water immersion (42.0 ± 0.3 °C) to nipple level. WALK comprised 60 min at 6 km/h, 7% incline, followed by 30 min at 6 km/h, 1% incline to prolong exercise and facilitate continued heat storage if Tc<39.5 °C after 60 min. RUN involved treadmill running at 69 ± 2% VO2peak. PaH and RUN continued until Tc reached 39.5 °C, volitional exhaustion or 60 min. Tc, heart rate (HR), perceptual responses, and concentrations of intestinal fatty acid binding protein (IFABP) and lipopolysaccharides (LPS) were assessed. Stepwise multiple linear regression was used to identify predictors of post-condition IFABP. Results Peak Tc was similar between PaH (39.3 ± 0.3 °C) and RUN (39.4 ± 0.2 °C, P = 0.944), and lower in WALK (38.2 ± 0.4 °C, both P < 0.001). Cumulative heat load assessed by area under the curve Tc≥38 °C was similar between WALK (36.4 ± 11.3 °C/min) and RUN (34.3 ± 7.5 °C/min, P > 0.999) but lower in PaH (25.7 ± 5.6 °C/min, P < 0.05 vs. WALK, P < 0.01 vs. RUN). IFABP increased in RUN (745 ± 432 pg/ml vs. 1855 ± 1465 pg/ml, P < 0.001) and WALK (767 ± 476 pg/ml vs. 1144 ± 995 pg/ml, P < 0.05), but not in PaH (848 ± 569 pg/ml vs. 870 ± 562 pg/ml, P = 0.916). Post-condition IFABP was higher in RUN than PaH (P < 0.01) and WALK (P < 0.05), and similar between PaH and WALK (P > 0.999). LPS decreased in all conditions (all P < 0.05). Body fat percentage, body mass loss and body mass index explained 15% of the variance in post-condition IFABP. Conclusions Intestinal epithelial injury occurred following exertional, but not passive hyperthermia, at matched peak Tc. This highlights that combinations of thermal, metabolic and mechanical stress drive GI injury rather than Tc elevation alone. Prolonged low-intensity exercise relevant to occupational exposures may incur sufficient cumulative heat load to induce subclinical intestinal injury. Interventions should consider managing exertional load alongside thermal strain to protect gastrointestinal health.