Gastrointestinal Paradigm of Exertional Heat Illness

Abstract

Exertional heat illnesses (EHIs) typically occur during vigorous physical activity eliciting high metabolic heat production, often in conditions restricting heat loss. They are commonly classified across a spectrum of increasing severity ranging from exertional heat exhaustion, to exertional heat injury and exertional heat stroke, but understanding of their aetiology is incomplete. There is growing interest in the potential role of the gastrointestinal (GI) system in EHI development (the ‘GI paradigm of EHI’), but relevant human data are lacking. This thesis comprises three investigations examining the putative role of the GI system in EHI aetiology.
Individuals who have suffered a recent EHI have previously been shown to be at an increased risk of developing a subsequent EHI. Study one investigated indices of GI barrier integrity, GI barrier damage, microbial translocation and inflammation in military service personnel (SP) who had suffered a recent (~4 months) EHI (patients). A cross-sectional cohort design was employed, with two independent groups (patients: n=29; matched controls: n=29), attending the Institute of Naval Medicine’s Heat Illness Clinic to undertake a heat tolerance assessment (HTA). Terminal thermoregulatory indices, perceptual indices, and markers of GI barrier integrity did not differ (p<0.05) between the groups in response to the HTA. However, a subset of participants in both groups were identified as heat intolerant (n=12) and demonstrated a reduced whole body sweat rate; these individuals also displayed increased plasma [sCD14] compared to heat tolerant individuals.
Study two used 16S rRNA gene amplicon sequencing to compare the composition of the GI microbiota between the recent EHI patient and control cohort. Overall, with the exception of a small difference in the Simpson index, there were no significant differences in the composition of the GI microbiota between groups. Furthermore, when comparing the composition of the GI microbiota between heat tolerant (n=46) and intolerant (n=12) individuals, we identified a reduction in the Firmicutes/Bacteroidota ratio in heat intolerant individuals, but no further differences were present in microbial diversity and the relative abundances of taxa at a Phylum down to Genus taxonomic level. Lastly, only two taxa showed significant associations with aspects of the thermal and GI response to exercise heat-stress.
The final Study investigated indices of the GI paradigm in SP who subsequently (within 3 days) developed an EHI. Using a unique prospective study design, we examined the composition of the GI microbiota and markers of GI barrier integrity in Royal Marine recruits prior to undertaking a six-mile speed march (6MSM) during which 79 individuals subsequently developed an EHI (n: 55 mild, 18 moderate, 6 severe EHI cases). EHI cases were pair matched by body mass index and cardiorespiratory fitness to control participants within the same troop who did not develop an EHI during the 6MSM. The GI microbiota and markers of GI barrier integrity did not differ between EHI cases and matched controls. These findings persisted with additional sub-group analysis constrained to only moderate and severe EHI cases, and sensitivity analysis excluding individuals reporting non-steroidal anti-inflammatory drug use or GI disorders.
Together, these studies demonstrate that there are limited large-scale differences in the GI microbiota composition and indices of GI barrier integrity between: i) SP who have suffered a recent EHI compared to matched controls; and ii) SP who subsequently develop an EHI compared to SP who do not develop an EHI during the same activity. This suggests that the GI microbiota and markers of GI barrier integrity are unlikely to precipitate the elevated EHI reoccurrence rates in recent EHI patients, and do not appear to increase predisposition to EHI development on this cohort. The evidence reported represents an important contribution to the body of knowledge and the putative role of the GI system in the aetiology of EHI.

Date of Award	1 Jul 2024
Original language	English
Awarding Institution	University of Portsmouth
Supervisor	Jo Corbett (Supervisor), Mike Tipton (Supervisor) & Sam Robson (Supervisor)