Differential Intestinal Epithelial Injury Following Passive and Exertional Hyperthermia

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 (T_c) 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.

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 T_c<39.5 °C after 60 min. RUN involved treadmill running at 69 ± 2% VO₂peak. PaH and RUN continued until T_c reached 39.5 °C, volitional exhaustion or 60 min. T_c, 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.

Peak T_c 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 T_c≥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.

Intestinal epithelial injury occurred following exertional, but not passive hyperthermia, at matched peak T_c. This highlights that combinations of thermal, metabolic and mechanical stress drive GI injury rather than T_c 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.