Abstract
sure to passive heat (acclimation) and exercise under hot conditions (acclimatization), known as heat acclimation (HA), are methods that athletes include in their routines to promote faster recovery and enhance physiological adaptations and performance under hot conditions. Despite the potential positive effects of HA on health and physical performance in the heat, these stimuli can negatively affect gut health, impairing its functionality and contributing to gut dysbiosis. Blood redistribution to active muscles and peripheral vascularization exist during exercise and HA stim- ulus, promoting intestinal ischemia. Gastrointestinal ischemia can impair intestinal permeability and aggravate systemic endotoxemia in athletes during exercise. Systemic endotoxemia elevates the immune system as an inflammatory responses in athletes, impairing their adaptive capacity to exercise and their HA tolerance. Better gut microbiota health could benefit exercise performance and heat tolerance in athletes. This article suggests that: (1) the intestinal modifications induced by heat stress (HS), leading to dysbiosis and altered intestinal permeability in athletes, can decrease health, and (2) a previously acquired microbial dysbiosis and/or leaky gut condition in the athlete can negatively exacerbate the systemic effects of
tolerance. Better gut microbiota health could benefit exercise performance and heat tolerance in athletes. This article suggests that: (1) the intestinal modifications induced by heat stress (HS), leading to dysbiosis and altered intestinal permeability in athletes, can decrease health, and (2) a previously acquired microbial dysbiosis and/or leaky gut condition in the athlete can negatively exacerbate the systemic effects of HA. Maintaining or improving the healthy gut microbiota in athletes can positively regulate the intestinal permeability, reduce endotoxemic levels, and control the systemic inflammatory response. In conclusion, strategies based on positive daily habits (nutrition, probiotics, hydration, chronoregulation, etc.) and preventing microbial dysbio- sis can minimize the potentially undesired effects of applying HA, favoring thermotolerance and performance enhancement in athletes. Keywords:acclimation/acclimatization, heat stress; gut microbiota; intestinal dysbiosis; intestinal permeability; athletes 1. Introduction Over the last decades, athletes have starting to include different strategies of passive and active exercise in hot conditions (passive heat) to promote recovery and thermo- tolerance in subsequent exercise in the heat [1–4]. Exposure to heat promotes adaptive responses of acclimation or acclimatization, depending on whether the exposure occurs in artificial (acclimation) or natural (acclimatization) warm environments [1]. Heat ac- climation/acclimatization, hereafter HA, is used among athletes to protect health and improve performance in hot environments [1]. Long-term HA strategies, which include regular passive or active heat exposure for more than 10 days, achieve the best results compared to short-term interventions [4]. To date, there have been a large number of protocols and guidelines described for long-term HA procedures [3–7]. During exercise in Microorganisms2024,12, 1160.
Microorganisms2024,12, 1160 2 of 15 the heat, premature exhaustion and shock due to heat stress (HS) can be common in athletes not acclimatized to heat and are the result of a complex combination of heat cytotoxicity (including endotoxemia from the gut), impaired coagulation, and systemic inflammatory response syndrome (SIRS), which is followed by deterioration of organ responses and ultimately, reduced physical performance. The prevention of heat stress is now considered to be more beneficial than treating the condition. Therefore, providing strategies that promote the prevention of premature heat fatigue would be of interest for athletes, coaches, and scientist. Biologically, prolonged and intense exercise elevates body temperature, promoting blood redistribution to active muscles, which reduces intestinal blood flow by 80% [8]. This effect promotes intestinal ischemia that exacerbates damage to the epithelial cells and tight junction proteins making up the intestinal mucosa’s physical barrier [9]. The gastrointestinal (GI) tract exhibits key functions in maintaining whole-body homeostasis and health. The GI tract is the organ directly responsible for absorbing nutrients, and it acts as a physical and immunological barrier against the entry of noxious compounds into the interior milieu [10]. Impairment of the gut barrier integrity is often involved in various GI and extra-GI diseases, resulting in reduced physical performance. On the other hand, the gut microbiota (GM) colonize the GI tract and develop multiple systemic functions for the host at digestive [11,12], metabolic [11,12], immunological [11–13],homeostatic [11,12,14–16] , and structural [11,12] levels. In fact, the GM is directly involved in maintaining the epithelial barrier integrity through bacterial activity, producing and synthesizing mucus and short-chain fatty acids (SCFAs) [11,12,17]. Thus, the GM interacts directly with the immune and neural systems through metabolites and nerves (gut–brain axis), modulating the inflammatory response, and preventing harm to the intestinal barrier [13]. Furthermore, the GM contributes to maintaining the appropriate intestinal pH, temperature, and oxygen levels for different structures of the intestine [11,12,14–16]. Maintaining a healthy gut microbiota can be achieved by maintaining a higher diversity, stability, and balance of the bacterial ecosystem [18]. For athletes, maintaining a healthy GM is key to promoting adaptive benefits
harm to the intestinal barrier [13]. Furthermore, the GM contributes to maintaining the appropriate intestinal pH, temperature, and oxygen levels for different structures of the intestine [11,12,14–16]. Maintaining a healthy gut microbiota can be achieved by maintaining a higher diversity, stability, and balance of the bacterial ecosystem [18]. For athletes, maintaining a healthy GM is key to promoting adaptive benefits that prevent aberrant responses such as those occurring during a state of gut dysbiosis, characterized by local inflammation, leaky gut syndrome, and impaired metabolic and endocrine functions [19]. In this regard, the therapeutic role of maintaining a healthy gut microbiota (GM) has also been reported in the prevention of heat stroke through the deterrence of systemic endotoxemia [20]. Conversely, the imbalance of the GM is defined and described in the literature as a dysbiosis that contributes to a worsening of the symbiotic functions in the host [17]. Such a condition can be reached following exposure to different stressful stimuli and negatively result from a life style that includes poor nutrition, exposure to toxics and pollu- tion, chronodisruption, certain acquired pathologies, and sedentarism [21]. An aberrant consequence of gut dysbiosis is leaky gut syndrome, in which intestinal permeability is impaired, resulting in the higher translocation of bacteria and toxins from the gut into the bloodstream (endotoxemia) [22–24]. Systemic endotoxemia results in a systemic inflam- matory and immune response that directly impairs health and physical performance [25]. Thus, the chronicity of systemic inflammation and immune overreaction can lead to a negative physiological spiral, compromising both the health and physical performance of athletes [26]. The pathophysiology occurring during heat exposure can be aggravated when athletes suffer from a state of GM dysbiosis. In this regard, Costa et al. [27] describe how improving the balance of the gut microbiota (GM) in athletes, including epithelial barrier health, could improve the systemic state during exercise in the heat, decreasing the inflammatory response and endotoxemia induced by the gut. In rats, Cao et al. [28] demonstrated that improving the gut microbiome balance and its functions in regards to gut barrier integrity (mucus, cell integrity, and selective permeability)
balance of the gut microbiota (GM) in athletes, including epithelial barrier health, could improve the systemic state during exercise in the heat, decreasing the inflammatory response and endotoxemia induced by the gut. In rats, Cao et al. [28] demonstrated that improving the gut microbiome balance and its functions in regards to gut barrier integrity (mucus, cell integrity, and selective permeability) induced protective properties under heat stress. The mucus layer acts as an important mechanism for pro- tecting the host against microbial invaders and contributes to the mutualism between the host and the microbes [29]. The loss of mucus layer thickness would be a consequence, as
Microorganisms2024,12, 1160 3 of 15 well as a precursor for both negative as maladaptive responses to HA and other physically elevated demands in athletes. Therefore, athletes must take into consideration their own systemic health [30], in- cluding their GM balance and the integrity of their GI functions prior to including highly specific training methods, such as HA. Future studies require the investigation of direct strategies that prevent and treat GI complications produced by extreme environmental conditions such as heat [31] or altitude [32]. Here, we investigate the direct consequences induced by a state of GM dysbiosis on maladaptive responses suffered by athletes exposed to HS. The main goal of the present study is to highlight the importance of maintaining a healthy GM balance in athletes as a therapeutic treatment, which can specifically contribute to the prevention of premature fatigue during HS exposure and exercise. 2. Heat Stress Stimulus and Gut Dysbiosis in Athletes The physical preparation of high-performance athletes is very difficult and includes repeated highly specific and intense stimulus (elevated consumption of simple carbohy- drates [30] and proteins [33], hypoxic exposure and training [34], and heat exposure and training [4]). Extensive evidence has shown that heat exposure (active and passive) can promote health and physical performance benefits [3,32–34]; however, the specific thresh- old that negatively affects health has not been completely explored. Until recently, most research on this topic has focused on how heat stress promotes intestinal alterations, such as burns, in patients with heat-related pathologies [35–37]. However, these specific inter- ventions require efficient systemic responses to maintain and/or improve physiological performance under such stress. The maintenance of the systemic health of athletes is the main factor for obtaining the benefits of these specific interventions [30]. For example, in a systemic context, where athletes experience a decline in health due to chronic stress, higher levels of immune response and inflammation increase the allostatic load and can induce more physiological damage, impairing physical performance. It is important, therefore, to understand the mechanisms that improve adaptive responses in both the short and long term, including a healthy GM and its communication
a systemic context, where athletes experience a decline in health due to chronic stress, higher levels of immune response and inflammation increase the allostatic load and can induce more physiological damage, impairing physical performance. It is important, therefore, to understand the mechanisms that improve adaptive responses in both the short and long term, including a healthy GM and its communication with the athlete’s organisms. The increased plasma endotoxemia from leaky gut syndrome is suspected to be an important etiological factor in the circulatory shock that accompanies premature HS intol- erance in humans [38]. The exposure to HS and maximal exercise aggravates endotoxemia in the context of impaired gut permeability, possibly due to the reduction of hepatic detoxi- fication. During HA and exercise, the reduction of portal vein blood flow, combined with thermally altered hepatocyte function, severely reduces the capacity to detoxify a surge of endotoxin [39]. The non-adaptive effects of HS on performance and health have been related to exacerbated cardiovascular, metabolic, and hormonal responses [7]. At the gut level, HS can lead to leaky gut syndrome, which is associated with intestinal ischemia. During HA and exercise, a systemic blood flow redistribution from splanchnic and renal vascular beds to the muscular and cutaneous vascular beds exists, ensuring an adequate energy and oxygen supply to the active muscles and facilitating heat dissipation [40]. However, gut ischemia and its consequent hypoxia increases metabolic stress [41], which directly alters the structure of the enterocyte membrane [22], involving tight junctions (TJs), which become damaged, allowing for the translocation of lipopolysaccharides (LPS) from Gram-negative bacteria (mainly proteobacteria) into the circulation [22]. Gram-negative bacteria found in the small and large intestine are harmful to the body due to an endotoxin unit located in the bacterial outer membrane [23]. This translocation of LPS from the luminal side to the bloodstream stimulates a systemic immune response characterized by the release of proinflammatory cytokines IL-6 and TNF-α[42]. It also activates innate immune production (circulating monocytes and tissue macrophages like Kupffer cells) of anti-inflammatory cytokines IL-1 [43]. This inflammatory response further affects tight junctions, which show increased leakage of bacterial
membrane [23]. This translocation of LPS from the luminal side to the bloodstream stimulates a systemic immune response characterized by the release of proinflammatory cytokines IL-6 and TNF-α[42]. It also activates innate immune production (circulating monocytes and tissue macrophages like Kupffer cells) of anti-inflammatory cytokines IL-1 [43]. This inflammatory response further affects tight junctions, which show increased leakage of bacterial LPS on the basolateral side [44]. Along with the cytotoxic
Microorganisms2024,12, 1160 4 of 15 effects of hyperthermia produced by HS and exercise itself, dehydration often exacerbates these effects, compromising the thermoregulatory capacity [45]. This situation further aggravates permeability, and the blood LPS concentration reaches a threshold that can trigger a systemic inflammatory response (SIR) (see Figure) [39]. Figure 1.Heat stress (HS) training and exposure promote ischemia in the intestine through the blood redistribution to active muscles and vascular vessels. The main goal of the body during HS is maintain homeostatic temperature. Gut dysbiosis is a negative health condition for the body, impairing symbiotic functions of the microbiota and aggravating intestinal dysfunctions, presenting as impaired gut permeability. Gut permeability dysfunction allows for the passage of endotoxins into the blood, increasing the systemic inflammatory response and reducing the time to exhaustion during exercise in a hot environment. Previous studies have shown that athletes who maintain a healthy gut homeostasis can perform physical activity free of adverse heat-related consequences, tolerating higher core temperatures (Tc), even up to 42 ◦ C [46–49]. In this context, research studies have proposed different preventive measures, focusing on minimizing the systemic effects of increased body temperature [50–52]. However, no previous studies have suggested that athletes who improve their GM health could preserve their intestinal functions and reduce the premature heat-shock and/or systemic failure induce by exacerbated endotoxemia and inflammation derived from the gut. These preventive factors related to gut health may play a crucial role in the pathophysiology of HS beyond the effects of heat stress, as suggested by previous research [26,53,54]. In this regard, Armstrong et al. [39] proposed that higher tolerance to moderate levels of LPS produced during HS and maximal exercise could be a
Microorganisms2024,12, 1160 5 of 15 plausible explanation for the superior tolerance to endotoxemia in athletes acclimatized to hyperthermia. In the short-term, acute HS appears not to affect the diversity and abundance of pro- tective commensal bacteria (those more favorable to host gut health, such asLactobacillus, Bifidobacterium,Streptococcus,Akkermansia muciniphyla,Faecalibacterium prausnitzii,Roseburia, orEubacterium) [55–58]. However, applying chronic passive and active heat during HA stimuli in athletes may aggravate leaky gut syndrome and potentiate systemic endotox- emia. This could trigger systemic inflammation similar to that observed in pathologies associated with heat stress and significantly impair physical performance (see Figure). Intestinal microorganisms are sensitive to changes in systemic temperature. The increase in internal temperature derived from exercise in HA could enhance the emergence of potential pathogens that would directly exacerbate dysbiosis, intestinal leaky gut syndrome, and consequently, systemic endotoxemia and inflammation (see Figure). It has been reported that each bacterium require a specific environmental milieu to live and growth adequately. In this regard, some pathogenic bacteria, such asEscherichia coliand other members of the Enterobacteriaceaefamily, are thermotolerant, able to survive at temperatures both cooler and warmer than those of the typical endothermic host.Yersinia enteropathogeniccan grow at temperatures close to 0 ◦ C [59], while laboratory strains ofEscherichia colican grow between approximately 8 ◦ C [60] and 42 ◦ C, and adapt to grow at temperatures of 48 ◦ C or higher [61]. Members of theProteobacteriaphylum are considered functionally flexible in response to various environmental stresses. Specifically, pathogens likeSalmonella,Yersinia, Pseudomonas, and pathogenicEscherichia coliuse host temperature as an environmental cue to upregulate the virulence genes [62–64]. These genes respond more strongly to fever-like temperatures, such as 42 ◦ C, than to temperatures below 37 ◦ C [64], and an enzyme in Pseudomonas aeruginosashows increased efficiency up to 45 ◦ C [64].Clostridioides difficile, another relevant intestinal pathogen, grows equally well at 37 ◦ C and 41 ◦ Cin vitro[65,66]. In a study using growing pigs subjected to chronic heat stress, intestinal dysbiosis and increased permeability were observed, characterized by an increase in the presence of potential pathogens likeAsteroleplasma,Shuttleworthia, andMycoplasma. Additionally, a suppression of beneficial bacteria species such asCoprococcusandAeriscardovia, which are
C [64].Clostridioides difficile, another relevant intestinal pathogen, grows equally well at 37 ◦ C and 41 ◦ Cin vitro[65,66]. In a study using growing pigs subjected to chronic heat stress, intestinal dysbiosis and increased permeability were observed, characterized by an increase in the presence of potential pathogens likeAsteroleplasma,Shuttleworthia, andMycoplasma. Additionally, a suppression of beneficial bacteria species such asCoprococcusandAeriscardovia, which are associated with intestinal immune function, was observed [67]. Figure 2.Heat stress can lead to gut dysbiosis through the elevation of certain thermotolerant bacteria, while reducing other beneficial bacteria. The reduction of blood perfusion during exercise produces ischemia hypoxia in the gut, possibly increasing the GM dysbiosis and exacerbating the effects of heat stress during exercise.
Microorganisms2024,12, 1160 6 of 15 3. Could Gut Health Improve Heat Stress Tolerance in Athletes? The use of biomarkers to monitor HS response (molecular, physiological, and behav- ioral) can be a valuable tool for assessing an athlete’s resilience under such conditions. To maintain homeostasis during HS, athletes fight to adjust their physiological and behavioral responses to positively adapt. The regular stimulus of heat exposure in athletes possibly alters the behavioral responses, including food and hydration intake, the frequency and duration of sleep, and normal activities, including resting. From a molecular perspective, biomarkers such as heat shock protein 60 [39] or interleukins [35] are being used to monitor the response to HS. Thus, GM analysis could also be used as a biomarker contributing to an early diagnosis of HS intolerance by detecting GM dysbiosis. [68]. The gut is one of the major target organs affected by specific interventions caused by exercise, altitude, nutrition, and heat stress. High-intensity exercise and HA promotes damage of the mucosal epithelia, increasing immune activity and leaky gut syndrome. Moreover, HS promotes changes in regards to GM diversity [69]. Recent studies have suggested that heat acclimatization improves physiological performance during HS through systemic responses, but this may also be related to GM adaptation [55]. It has been shown that after HA, a significant decrease in potentially pathogenic bacteria occurs, whereas beneficial bacteria increase significantly [9,55,70]. Therefore, optimizing beneficial bacterial phenotypes from the GM (for example, higher levels of bacterial precursors of efficient gut permeability, short-chain fatty acid production, secondary bile acid production) confers potential benefits for responding and adapting to HS and physical exercise. Interventions focused on precise nutrition and probiotic intake [55,71] could be necessary when athletes include heat exposure during their training and competitive routines. 3.1. Specific Nutrition and Hydration Balance to Improve Gut Health and HA Tolerance in Athletes The loss of bacterial homeostasis in the gut (dysbiosis), with the presence of impaired epithelial permeability (leaky gut syndrome), is a catastrophic condition for athletes because it can increase their risk of suffering premature fatigue during HA and/or maximal exer- cise [72]. Therefore, improving and
Description
The study highlights the importance of gut health for athletes' performance in heat.