4. Discussion
gut damage, gut injury, intestinal injury, ’
SYSTEMIC DISEASE, ADVERSE EFFECTS, ADHESION, OXIDATIVE STRESS, PATHOGENESIS
Here, we provide evidence that (1) markers of intestinal permeability are significantly increased during intensive exercise compared to moderate exercise and (2) chronic intake of dark chocolate can counteract impaired intestinal permeability induced by intense exercise during elite football players’ training sessions. In vitro, we demonstrated that polyphenols from dark chocolate can mitigate oxidative stress and epithelial permeability induced by LPS, which harms the intestinal barrier integrity.Several pieces of evidence have described that intensive physical exercise has an impact on gut health and integrity. However, there is no detailed information regarding the appropriate exercise dose–response thresholds that do not generate adverse effects for the intestinal mucosa; it is known that the degree to which intestinal permeability is induced by acute or prolonged exercise is directly related to the duration and intensity of exercise, as well as the recovery between sessions [The results of a recent meta-analysis [In our study, we found that elite athletes, participating in highly intense professional training programs, displayed increased circulating levels of zonulin and occludin, two biomarkers of impaired gut function, compared to amateur athletes engaged in moderate-to-intense exercise. Moreover, we found increased levels of serum LPS, consistent with increased gut permeability. This association was also confirmed by the positive correlation between LPS, zonulin, and occludin.The intestinal barrier has a critical function in human health, with a role in the pathogenesis of intestinal and systemic diseases. Because of the downregulation of intestinal adhesion proteins induced by gut dysbiosis, LPS caused increases in reactive oxygen species (ROS) production [As athletes’ training and competition schedules increase, it is important to identify effective non-invasive strategies that are able to modulate intestinal permeability. In general, there is growing evidence that dietary supplementation with polyphenols derived from natural products can improve physical performance, with mechanisms that are most likely related to antioxidant and vascular effects. We previously demonstrated that polyphenol-rich food supplementation had a positive effect on high-intensity training elite athletes’ antioxidant status [In our study, we demonstrated that chronic supplementation with dark chocolate, which is a high source of polyphenols, reduces biomarkers of gut permeability induced by intense exercise compared to non-supplemented athletes.The beneficial effects induced by polyphenols derived from dark chocolate were also confirmed in vitro, on Caco-2 cells, by analyzing the protein system that is crucial in ensuring the integrity of tight junction structures. Tight junctions have a composite molecular structure consisting of multiple protein complexes made up of several major types of proteins, including claudin, occludin, and the intracellular scaffold zonula occuldin proteins (ZO-1, ZO-2, and ZO-3). Tight junctions can be regulated by several factors, including different ROS, especially HOur study has limitations and implications. The fact that polyphenol supplementation modulates gut permeability in elite athletes during intensive exercise provides novel insight into a nutrition-related strategy to counteract gut injury and potentially to reduce the cardiovascular risk induced by gut-derived LPS [We must acknowledge that we have not performed a direct evaluation of gut permeability. Therefore, the increased indirect biomarkers observed only indicate an intestinal injury and we only speculate that increased LPS could induce gut damage in this setting. Second, we partially evaluated the mechanisms by which polyphenols restore gut function. Previous studies indicate that polyphenols exert their biological activities in the gut at several levels. Polyphenols can modulate, through their metabolites, the intestinal microbial ecosystem, a function that could explain the reduction in LPS observed in elite athletes after supplementation. Moreover, they can downregulate inflammatory genes, such as NF-κB, and cytokine production and up-regulate antioxidant genes [