Gastrointestinal complaints are often reported during ascents to high altitude (>2,500 m), though their etiology is not known. One potential explanation is injury to the intestinal barrier which has been implicated in the pathophysiology of several diseases. High-altitude exposures can reduce splanchnic perfusion and blood oxygen levels causing hypoxic and oxidative stress. These stressors might injure the intestinal barrier leading to consequences such as bacterial translocation and local/systemic inflammatory responses. The purpose of this mini-review is to 1) discuss the impact of high-altitude exposures on intestinal barrier dysfunction and 2) present medications and dietary supplements which may have relevant impacts on the intestinal barrier during high-altitude exposures. There is a small but growing body of evidence which shows that acute exposures to high altitudes can damage the intestinal barrier. Initial data also suggest that prolonged hypoxic exposures can compromise the intestinal barrier through alterations in immunological function, microbiota, or mucosal layers. Exertion may worsen high-altitude-related intestinal injury via additional reductions in splanchnic circulation and greater hypoxemia. Collectively these responses can result in increased intestinal permeability and bacterial translocation causing local and systemic inflammation. More research is needed to determine the impact of various medications and dietary supplements on the intestinal barrier during high-altitude exposures.

Using an experimental model of extreme heat exposure that incorporates brief periods of light physical activity to simulate activities of daily living, the extent of thermal strain reported herein more accurately represents what would occur during actual heatwave conditions. Despite matching metabolic heat generation and environmental conditions, we show that older adults have augmented core temperature responses, likely due to age-related reductions in heat dissipating mechanisms.

Conditions characterized by muscle wasting such as cachexia and sarcopenia are devastating at the individual level, and they place a profound burden on public health. Evidence suggests that inflammation is likely a mechanistic contributor to the pathogenesis of these conditions. One specific molecule, lipopolysaccharide, has gained attention due to its role in initiating inflammation. Toll-like receptor-4 is the primary receptor for lipopolysaccharide and has been shown to be implicit in the downstream proinflammatory response associated with lipopolysaccharide. Importantly, Toll-like receptor-4 is expressed in various cell types throughout the human body such as leukocytes and skeletal muscle fibers and may have site-specific effects that contribute to muscle wasting conditions based on the location in which activation occurs. Accordingly, reducing proinflammatory signaling at these locations may be an effective strategy at mitigating muscle wasting. Regular exercise training is believed to elicit anti-inflammatory adaptations, but the mechanisms by which this occurs are yet to be fully understood. Understanding the mechanisms by which Toll-like receptor-4 activation contributes to muscle wasting and how exercise affects this may allow for the development of a nonpharmacological therapeutic intervention. Therefore, in this review, we summarize the current understanding of the lipopolysaccharide/Toll-like receptor-4 axis in leukocytes and skeletal muscle fibers on the pathogenesis of muscle wasting conditions and we critically examine the current evidence regarding the effects of exercise on this axis.