Interactions of Gut Microbiota, Endotoxemia, Immune Function, and Diet in Exertional Heatstroke

Abstract

Exertional heatstroke (EHS) is a medical emergency that cannot be predicted, requires immediate whole-body cooling to reduce elevated internal body temperature, and is influenced by numerous host and environmental factors. Widely accepted predisposing factors (PDF) include prolonged or intense exercise, lack of heat acclimatization, sleep deprivation, dehydration, diet, alcohol abuse, drug use, chronic inflammation, febrile illness, older age, and nonsteroidal anti-inflammatory drug use. The present review links these factors to the human intestinal microbiota (IM) and diet, which previously have not been appreciated as PDF. This review also describes plausible mechanisms by which these PDF lead to EHS: endotoxemia resulting from elevated plasma lipopolysaccharide (i.e., a structural component of the outer membrane of Gram-negative bacteria) and tissue injury from oxygen free radicals. We propose that recognizing the lifestyle and host factors which are influenced by intestine-microbial interactions, and modifying habitual dietary patterns to alter the IM ecosystem, will encourage efficient immune function, optimize the intestinal epithelial barrier, and reduce EHS morbidity and mortality.

Heat Adaptation in Military Personnel: Mitigating Risk, Maximizing Performance

“…A secondary function of the gastrointestinal tract is in the prevention of translocation of potentially harmful luminal antigens into the systemic circulation (Camilleri et al, 2012;Wells et al, 2016). Exercise can adversely disrupt the gastrointestinal barrier integrity (Lambert, 2004) in proportion to the amount of thermal stress (Costa et al, 2017b;Pires et al, 2017) so causing leaking of gram negative bacteria into the intravascular space (Lambert, 2004;Yeh et al, 2013) potentially causing exertional heat stroke (Armstrong et al, 2018;Lim, 2018). Mechanisms include a transient gut hypoxemia secondary to blood shunting from the viscera to exercising muscles causing an overwhelming efflux of endotoxins in circulation (Pyne et al, 2014) and systemic inflammatory responses.…”

The Gastrointestinal Exertional Heat Stroke Paradigm: Pathophysiology, Assessment, Severity, Aetiology and Nutritional Countermeasures

“…A simplified schematic of the GI EHS paradigm is shown in Figure 1. Interested readers are referred to several detailed reviews on this topic [1,36,37].…”

“…A simplified schematic of the GI EHS paradigm is shown in Figure 1. Interested readers are referred to several detailed reviews on this topic [1,36,37]. To date, direct investigation into the pathophysiology of the GI EHS paradigm has been limited, which is perhaps surprising given the substantial morbidity/mortality associated with the disease.…”

“…In consideration of these issues, numerous consensus documents have been published that provide occupational guidance on effective EHS management (e.g., [32][33][34][35]), though predominately take a thermoregulatory approach to disease management (e.g., cooling, heat acclimation). A gastrointestinal paradigm of EHS pathophysiology (also known as "endotoxemia" or "heat sepsis") has gained momentum as a secondary pathway through which to focus EHS management [36,37], though consensus documents detailing this approach are currently unavailable.…”

“…The immunological barrier comprises crypt paneth cells within the epithelial monolayer that secrete antimicrobial proteins, and gut associated lymphoid tissue within the lamina propria that stimulate multiple effector immune responses. In healthy individuals, the GI tract is largely effective in preventing GI microbial translocation (MT) into the systemic circulation [40], however, growing evidence hypothesises a fundamental role of GI MT within the pathophysiology of EHS [36,37]. The focus of this review is to evaluate: (1) the GI paradigm of EHS; (2) GI barrier integrity assessment techniques; (3) typical GI barrier integrity responses to exertional-heat stress; (4) the aetiology of GI barrier integrity loss; and (5) nutritional countermeasures to support GI barrier integrity during exertional-heat stress.…”