A Narrative Hypothesis: The Important Role of Gut Microbiota in the Modulation of Effort Tolerance in Endurance Athletes

In recent years, research on the connection between the gut microbiota (GM) and the central nervous system (CNS) has been growing exponentially [1,2], particularly in its relation to health, physical performance, and cognitive processes related to perception, emotions, and pain [3,4,5]. Until now, only a limited number of studies have reported the interaction between the GM and the brain's emotions, perceptions, and sensations. Thus, no previous studies have hypothesised on the possible bidirectional influence existing between endurance exercise and the GM-CNS axis, which modulates fatigue and unpleasant sensations [1,6]. The primary communication networks between the gut and brain involve neural, endocrine, and immune pathways, encompassing the central, enteric, and autonomic nervous systems, as well as the hypothalamic–pituitary–adrenal axis. The GM can modulate the enteric nervous system response through the excitability of the nervous system, as well as the production of metabolites that enable signals to reach the CNS via the vagus nerve [7]. The GM, composed of a complex community of microorganisms, interact with the vagus nerve in the passage of digestive material [8] and in the regulation of gut hormones, neurotransmitters, and short-chain fatty acids (SCFAs) [8,9,10]. Therefore, individual differences and chronic changes in the GM profile may influence the cognition, perceptions, and sensations of the host. Some investigations have described that exercise in humans also increases neurogenesis and alters the microbiota profile [11].

Endurance exercise involves the ability to sustain a specific type of physical activity, such as running, cycling, or swimming, for a prolonged period, where intensity and duration increase, perceived effort rises, and fatigue levels become limiting to continue the activity. The physiological changes that occur during long endurance activities, affecting different systems such as cardiovascular and respiratory, metabolism, thermoregulation, and acid–base balance, contribute to altered perceptions. For this reason, training routines contribute to elevating sensitisation, the neuronal plasticity that occurs in response to prolonged fatigue, pain, and discomfort stimuli during intense efforts, even over several days [8]. Therefore, the globality of training stimulus, supported by endurance athletes, focuses on improving, on the one hand, physiological performance, and, on the other, enhancing sensitivity to tolerating discomfort and unpleasant sensations.

The hardness perceived during endurance exercise may contribute to increased sensitisation for peripheral tissues, as well as GM adaptation in athletes. The present hypothesis describes how promoting a higher effort sensitisation from peripheral and central tissues adaptively changes the abundance of specific gut bacteria related to brain perceptions (see Figure 1). Overall, in response to physical and cognitive stress, two different regulatory systems are activated: (1) the sympathetic–adrenomedullary and hypothalamic–pituitary–adrenal axes [8,12], and (2) the autonomic nervous system (ANS) [13]. Throughout these processes, the intestine is particularly important due to its direct influence on the regulation of the CNS, among other factors. Not surprisingly, there is increasing interest in research on GM and the brain axis, as well as their various connections with health, physical performance, and cognitive processes related to perception, emotions, and pain [3,4,5]. Recently, several publications have reported on the implications of GM on physiological and cognitive functions [1,6]. Still, data are largely lacking on how gut health can directly influence endurance performance through regulated emotions and tolerance to discomfort and fatigue.

Notably, it has been suggested that interventions enhancing GM diversity could positively impact endurance performance [14] and, in parallel, stimulate the production of metabolites such as NTs and other molecules involved in modulating perceptions and, consequently, tolerance to fatigue [15,16,17]. Instead, a GM imbalance may lead to poor well-being from leaky gut syndrome, which includes chronic low-grade inflammatory conditions, emotional instability, dysregulation of neurotransmitters, chronic fatigue, and even depression, all of which may impair athletic performance and tolerance to fatigue [18,19].

In this article, we reviewed the current scientific evidence on the relationship between endurance exercise and GM modulation in CNS perceptions. In addition, we discussed whether there exists a possible GM profile that improves higher effort tolerance. The main goal of the present article was to explore the hypothesis based on how hardness training in athletes could influence the GM ecosystem, alter sensory control through the autonomic nervous system, and influence additional gut metabolites in the blood and achieving the brain. The current work aimed to broaden perspectives in the field of sports science by suggesting that GM composition plays an important role in modulating perceptions during endurance performance.

The factors limiting endurance performance have traditionally focused on understanding how cardiovascular, metabolic, and muscular adaptations are produced [20]. The central (mental) regulation and the control of peripheral afferences from specific locomotor and visceral tissues that limit endurance performance through perceptions remain less studied. Human feeling includes the expression of body perceptions, emotions, and the modulation of systemic afferences. In the complex interplay of all these influences, the gastrointestinal tract and the GM, particularly, are relevant components influencing higher cerebral functions and behaviour [21,22,23]. In this regard, the gut metabolomic dialogue with the brain is essential for regulating perceptions and sensations [24], acting as both an autocrine, paracrine, and endocrine organ. In addition, the relationship between endurance exercise and this malleable organ, composed of the GM, could be very important to modulate physiological perceptions related to physical effort tolerance.

In such a case, discomfort and fatigue represent an individual and subjective perception involving nociception and nociplasticity [25,26]. In some cases, a higher capacity for tolerating discomfort during endurance exercise or other activities can explain why some individuals achieve better physical performances than others [27,28,29]. Hence, pain and discomfort coping is an integral part of athletic preparation that develops athletic character [30,31,32,33,34,35,36,37,38] in endurance athletes [33,39,40,41,42,43,44,45,46,47] or combat fighters [48], compared to power athletes [49].

The "individual limit of sensory tolerance" [28,29,50,51,52] has been proposed to describe the point at which individuals recognise their limit based on fatigue, pain, or effort [53], and can be improved following several weeks of intense training [44,54]. Pain, defined as the unpleasant, noxious perception that affects mood, social life, and overall quality of life, is a significant limiter of physical activity and quality of life. The individual threshold of pain is subjective, involving not only nociception but also emotional, cognitive, and social components [25]. During maximal endurance activities, athletes feel unpleasant sensations described with comments such as the following: "I cannot continue the race at this pace", "exercise was hard", "I never feel good", "legs do not work", etc. This effort fatigue is initiated by the activation of nociceptors that populate peripheral organs, such as skin, muscles, bones, joints, and deep visceral tissues [25,55]. Acute pain can contribute to modulating immune responses and protect organisms; however, chronic and sensitive thresholds in the nervous system can lead to elevated nociceptive activation, making organisms more sensitive to minimal immune reactions. Previous studies in clinical medicine have linked the composition of the gut microbiota to a higher incidence and progression of hyperalgesia and pain in certain chronic pathologies and treatments, such as chemotherapy [56].

Adaptive mechanisms for increasing pain and discomfort tolerance primarily depend on the stimulation of the interoceptive system, which is interconnected with the brain and integrated into the interoceptive consciousness [57,58,59]. The interoceptive system is an essential peripheral governor, constantly sensing physiological changes that trigger homeostatic thresholds for internal perceptions, emotions, pain, temperature, oxygen, sensory touch, muscle tension, discomfort, and intestinal sensations. These sensations are processed in the brain as an integrated interoceptive conscience [57,58,59]. As depicted in Figure 2, physiological afferences processed by the brain from peripheral organs and tissues transfer a consciousness of the internal body state during physical activities [60]. Thus, the operation of the interoceptive system is a highly relevant topic of research interest for manipulating perceptions and cognitive responses in conditions of effort, pain, or discomfort [61].

The intensity and duration of endurance exercise imply metabolic alterations that modify the neural response in the motor cortex, resulting in an increase in exertion from a perceptual perspective of sensations [62,63]. Previous studies have suggested that GM can modulate the neural system originating from the intestines and may influence pain thresholds in the brain, which are related to various systemic conditions [3,64,65]. The GM is capable of activating nociceptors [66], altering mediators of inflammation, and inducing phosphorylation in certain receptors and ion channels of sensory neurons, which can result in peripheral sensitisation [65]. Under this premise, the chronic stimulus of endurance exercise and other specific routines, such as nutrition and hydration, changes the GM profile individually. Therefore, the individual sensitive perceptions in a complex system of the body include the afferences derived from the gut through neural, chemical, and molecular signals.

During maximal endurance exercise, the physiological demands increase proportionally. The brain acts mainly in two protective ways: (1) monitoring biological vital signals from specialised cells for oxygen, temperature, vascular pressure, etc., and (2) producing neural perceptions according to the individual thresholds (set-points) that are derived from afferent discharges from organs and tissues to optimize the intensity of exercise. In addition, gut–brain communication is crucial in regulating afferent responses related to all stimuli arising from immune responses, inflammatory pathways, and metabolic efficiency [67], as well as systemic organs (see Figure 2). With regular endurance training, the different systemic thresholds can alter their grade of tolerance as an adaptive vital mechanism; if it is positive, athletes can perform at higher exercise intensities because their physiological and perceptual limits are increased based on their brain perception tolerance.

Concomitant changes that occur during exercise alter oxygenation, temperature, and metabolic activity, which directly affect gut microenvironments and thereby impact the gut microbiota [68]. The important role of the GM during physical failure is considered due to its modulatory effect on metabolic digestion, the immune system, systemic inflammation, and endocrine function, which involves regulating NTs and hormones related to perceptions, emotions, and sensations [1,6,69]. Here, we hypothesise that tolerance to pain, fatigue, and discomfort may be linked, in part, to intestinal barrier health, damage, and its biological function of permeability. This premise is based on the concept that the gut microbiota can directly or indirectly modulate peripheral sensitisation underlying chronic afferent pain or unpleasant sensations through multiple mediators, including the microbial by-products (e.g., PAMPs), metabolites (e.g., SCFAs, Bile Acids), and neurotransmitters (e.g., GABA) that are released. In this regard, athletes who are more sensitive to pain and effort sensations may be more susceptible to dysregulation of neurotransmitters and may experience GM dysbiosis [70]. In this case, in response to exercise demands, the GM may be unable to produce and maintain a certain threshold of SCFAs and NTs in the brain [70,71] to counteract the cognitive demands of discomfort [72] (Figure 3). Hence, in this regard, it can be hypothesised that improved intestinal health derived from a positive GM profile might positively impact the higher tolerance of sensory limits and effort perceptions in the long term. Therefore, the metabolite dialogue between bacteria and host neural pathways would be crucial in stimulating synaptic plasticity, an essential component of the microbiota–gut–brain axis, and in modifying the neural thresholds of tolerance to fatigue or discomfort [73]. To modify neuronal perception and sensitivity, it is hypothesised that physical and functional changes at the level of individual connections between neurons have occurred [74].

As a premise of the present hypothesis, it has been postulated that the GM profile in each individual may differ depending on the perceptions that evolve from acute to chronic neuropathic injuries, accompanied by pain and impairments in functional performance in athletes [75,76]. Regarding osteoarthritis pain, for example, increases in Streptococcus species were associated with knee osteoarthritis [77], while Coprococcus species were reduced in individuals with widespread chronic pain [78]. Recently, it was demonstrated that the levels of Bacteroides were lower in subjects with reduced tolerance to neuropathic pain. Conversely, the abundance of Prevotella was increased in subjects with higher tolerance to pain compared to those with lower levels [64]. Wang et al. [79] reported a reduced abundance of Bacteroides and Faecalibacterium in subjects with neuropathic pain, but Escherichia—Shigella, Lachnoclostridium, Blautia, Megasphaera, and Ruminococcus torques were elevated. Lower levels of Faecalibacterium prausnitzii have been correlated with a higher severity of osteoarthritis in older female adults [80]. Still, higher concentrations have been associated with antinociceptive effects in a rat model of irritable bowel disease [81]. These results, in summary, indicate that the GM composition can change drastically in response to injuries and chronic pain due to the higher inflammatory state in the tissues, which directly increases neural sensitivity [82]. However, whether GM dysbiosis is the consequence of the onset of nociceptive pain has not been elucidated, and it is unknown whether systemic pain, fatigue, and/or negative afferences would be modulated through the gut–brain connection.

The intensity and duration of endurance exercise suggest that substrate homeostasis changes during the activity and directly impacts central command in the motor cortex, thereby increasing effort perception [62,63]. The perceptions associated with energy homeostasis include the regulation of blood pH and the acid–base equilibrium, which is altered during exercise, leading to increased acidosis. In the intestines, the pH is slightly acidic in the caecum but approaches neutrality in the colon [83]. In the intestines, abnormal pH, promoted by chronic metabolic acidosis due to nutritional habits and intense endurance exercise, may increase the risks of epithelial damage and adverse changes in the GM composition of the colon [84]. The stability of colonic pH appears essential for regulating mucosal integrity, including bicarbonate and lactate production, the bacterial fermentation of carbohydrates, and the mucosal absorption of SCFAs [84]. Therefore, the inefficiency of the intestines in regulating blood pH may negatively affect endurance performance and metabolic efficiency. In this regard, some evidence has reported that certain bacteria (Veillonella atypica) may reduce lactate during exercise and increase endurance performance [85,86]. On the contrary, the GM composition that can improve the commensal bacteria to produce SCFAs decreases gut pH, and the transformation of primary to secondary bile acids reduces acidification [87,88].

Signalling molecules derived from the GM include SCFAs, NTs, gut hormones and peptides. The NTs' influence on neuronal activity is promoted by neuromodulatory molecules, such as dopamine, noradrenaline, serotonin, and GABA, produced by a wide array of bacteria [71]. Additionally, the gut microbiota was shown to play a significant role in the metabolism of tryptophan, which is synthesised mainly in the gut [71]. Considering the important role of the GM in NT and SCFA synthesis, we propose different specific bacteria and genera that have been proposed to produce these molecules (see Table 1).

In this narrative review, we conducted a search of scientific databases, including PubMed and Google Scholar, using the following terms and keywords: gut microbiota, physical exercise, endurance exercise, perceptions, fatigue, pain, discomfort, and nervous system. We included in Table 1 phenotypes related to specific target bacteria and genera that have been described as modulators of different neuromodulators involving NTs and SCFAs. Regarding phenotypes (dopamine, serotonin, acetylcholine, GABA, noradrenaline, emotional balance, butyrate, and propionate), references in such cases describe specific bacteria found to be related to these metabolites. We excluded articles that did not consider the relationship between the GM and the brain axis, as well as its relationship with perceptions and emotions.

The adaptive biological responses that we are building during our life depend on the most stimuli supported. In this regard, the maximal physiological stimuli supported during exercise by athletes and the general population differ largely. Thus, nutrition strategies associated with exercise in athletes promote changes in their GM in comparison with the general population. The differences between the GM of athletes (even comparing athletic level, elite and sub-elite) and the general population have been demonstrated. In fact, greater GM diversity is related to better endurance performance in elite athletes [246,247,248].

Athletic training and competition coexist with an ample range of sensations and perceptions of fatigue and discomfort. Previous studies have described how fatigue creates specific neural networks and learned feelings associated with physiological limits achieved during exercise [46,249,250]. The maintenance of long periods of tachycardia, hyperventilation, hyperthermia, dehydration with alterations on metabolism homeostasis, and inflammatory processes after exercise change perceptions and thresholds of tolerance on intensity and volume. In these conditions, these perceptions and sensations possibly are not supported by the general population with lower tolerance.

An important goal of athletes is stimulating tolerance to physiological limits and improving fatigue thresholds to reach greater performance in the final and decisional moments of competition. The link between the brain and systemic organs is key to elevate tolerances of discomfort related to heat, hypoxia, metabolic acidosis, or muscular soreness. Although it could be considered not directly related to fatigue, the gut microbiota specialization in athletes possibly provides NTs, SCFAs, and endocrine molecules supporting the brain modulation of neural networks. In fact, the neuronal loop of synapsis related to perceptions and emotions is connected to different molecules such as NTs derived from microbiota [73]. Therefore, a basic threshold for tolerating harder perceptions of discomfort could relate to the specialized GM production of neural metabolites. The specific nature of exercise determines nutrition, absorption, and substrate uptake during and after physical activity. In this regard, providing specific nutrients to feed a favourable GM must be a main goal for athletes but also in the general population. Some studies have postulated a direct correlation of fatigue tolerance in athletes with better physical performance [251,252]. The better effort regulation, self-control, and executive functions such as inhibitory control in athletes due to athletic training increase willpower by changing the connectivity between brain structures [253] through the action of neurotransmitters in the CNS [254].

The hypothesis described here supports the idea that greater dopaminergic activity in athletes in comparison with sedentary subjects can enhance motivation and tolerance to discomfort, increasing performance. Reaching a richer and more diverse GM in athletes in comparison with sedentary subjects would improve the abundance of short-chain fatty acid (SCFA)-producing bacteria contributing to the support of brain activity related to fatigue [255,256].

Precision nutrition approaches are being developed to provide comprehensive and dynamic nutritional recommendations tailored to individual variables, including microbiota, health status, and dietary patterns [257]. Generally, microbiota-based precision nutrition approaches seek to optimise GM and its modulating ability. In this regard, probiotics-based precision nutrition has been preliminarily explored to modulate the GM–brain axis using mainly probiotics [258], which are defined as live microbes that, when introduced in adequate quantities, confer health benefits on the host [259]. Furthermore, according to the influence of probiotics reported in other areas, such as against several GM dysbiosis conditions, or the positive effect, even in clinical trials, on chemotherapy side effects [260] and infections [261], we could hypothesise their positive results in sports, performance, and effort tolerance-related areas in the future. However, despite promising results, the consumption of probiotics in food and/or supplements has shown a common limitation in bioavailability and effect duration, regardless of the area of application, as they are not maintained in the intestine [262].

To address this limitation, microbiome-based precision nutrition is recommended, including probiotics and prebiotics to promote the growth of beneficial gut microbes, thereby favouring the natural development of the GM and potentially extending its metabolic effects [263]. In other words, combining probiotics and prebiotics produces the first bioactive metabolites directly in the human gut. Secondly, stimulating target bacteria not only to colonise but also to maintain themselves in the intestine, consequently, has a potential long-term effect.

Although the International Society of Sports Nutrition (ISSN) concluded that probiotics have strain-specific effects in athletes [264], most studies associate effort tolerance-related phenotypes with specific bacteria at the genus or species level (see Table 1). Therefore, selecting target bacteria associated with effort tolerance-related phenotypes should be done by prudent criteria and should be investigated in the future.

In summary, current evidence allows for the description of target bacteria with some of the most functionally evidenced effort tolerance-related phenotypes associated with neurotransmitters and gut metabolites. In this sense, several studies have associated different bacteria with neurotransmitter regulation, specifically regarding dopamine [71,89,90,91,92,93,94,95,96,97,98,99,100], serotonin [71,89,90,91,92,93,94,101,102,103,104], acetylcholine [71,89,91,92,105,106,107,108,109,110], GABA [71,91,92,93,111,112,113,114,115,116,117,118,119], and noradrenalin [71,91,92,93,98,120] (see Table 1). Similarly, there is increasing evidence of the contribution of specific bacteria to emotional balance [98,103,114,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139]. The GM influence on its phenotype appears to be related, at least in part, to neurotransmitter regulation due to the reported bacteria's psychoactive ability; therefore, they have been preliminarily selected as target bacteria. On the other hand, as previously reported, the SCFAs' pivotal role, specifically butyrate [140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174] and propionate [147,158,160,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200] (see Table 1), in the overall functionality of the GM, and potentially in effort tolerance, is strongly supported by the scientific literature.

It is worth noting that part of the current scientific evidence on a bacterium's ability to produce a specific metabolite is based on in vitro studies. In vitro studies are essential for generating knowledge, but they are insufficient for determining whether a bacterium behaves the same way in a real biological system. To assess the potential of a bacterium on human health, in vivo studies must be performed. For example, to determine if a bacterium meets the requirements of a potential probiotic strain, various in vitro tests are first conducted. Following this, in vitro and in vivo safety assessments, clinical trials, and in vivo efficacy assessments are conducted to ensure the product's safety and effectiveness in humans. There is no universal international standard to determine the safety of a probiotic for humans. Suppose a bacterium is considered safe for humans. In that case, it is classified as "Generally Recognised as Safe" (GRAS) by the United States Food and Drug Administration, or it is included in the "Qualified Presumption of Safety (QPS) list" by the European Food Safety Authority (EFSA) [265].

The bioavailability of GM key metabolites, neurotransmitters, and neuromodulators is affected by the cooperative and competitive relationships between bacteria within the microbial community. Cooperative relationships primarily refer to cross-feeding, where a product generated by one bacterium is utilised as a substrate by another [266]. There is an example of bidirectional cross-feeding between target bacteria Akkermansia muciniphila and Eubacterium hallii. A. muciniphila degrades host mucus and generates 1,2-propanediol that supports the growth of E. hallii. In return, E. halli produces pseudovitamin B12, which is used by A. muciniphila as a cofactor for converting succinate to propionate [151]. Bacteria compete to utilise the same energy resource, as observed for target bacteria A. muciniphila and Bacteroides thetaiotaomicron, which are both mucolytic [151,267].

The final target-bacteria selection is detailed in Table 1, indicating which bacteria have been associated with each effort tolerance-related phenotype and the corresponding literature references in each case. As can be seen, there is currently abundant and coherent scientific evidence regarding effort tolerance-related phenotypes and GM. Interestingly, some target bacteria have been associated with regulating more than one phenotype, such as Streptococcus thermophilus and Lactobacillus plantarum, both of which are involved in regulating acetylcholine, dopamine, and serotonin, and the latter is also associated with regulating GABA (Table 1). In addition, it is noteworthy that 17 of the 65 target bacteria listed in Table 1 are considered probiotics and are included in the revised list of microorganisms, with QPS-recommended microorganisms, for safety risk assessments carried out by the EFSA (https://www.efsa.europa.eu/en/topics/topic/qualified-presumption-safety-qps↗, accessed on 26 July 2025). The target bacteria included in the EFSA list are Bifidobacterium (B. adolescentis, B. animalis, B. bifidum, B. breve, and B. longum), Lactobacillus (L. acidophilus, L. brevis, L. casei, L. delbrueckii, L. helveticus, L. paracasei, L. plantarum, L. reuteri, L. rhamnosus, L. salivarius, and L. lactis), and Streptococcus thermophilus.

Therefore, we propose that these types of target bacteria have a high potential to influence effort tolerance and overall health positively, and are especially promising as targets in microbiome-based precision nutrition. Hence, a microbiome-based precision nutrition approach is proposed for effort tolerance-related GM optimisation (comprising phenotypes related to the regulation of the neurotransmitters dopamine, serotonin, acetylcholine, GABA, and noradrenaline, as well as emotional balance and the SCFAs butyrate and propionate).

Despite the strong evidence presented here regarding the potential of microbiome-based precision nutrition, the practical application of this food recommendation should be tested in future longitudinal studies, where different individuals are analysed before and after a precision nutrition intervention to improve effort tolerance by GM in the mid- to long-term. Although it is possible to change the composition of the microbiota through food in the short term, the objective should be to maintain these changes in microbiota composition [268] and, consequently, that the potential benefit in effort tolerance would be durable. In this regard, a microbiome-based precision nutrition approach could facilitate the individual identification of target diet components by a nutrition professional, who must consider the specific requirements of each person due to food allergies or incompatibilities between specific diet components and particular medications or treatments. The present investigation of this topic is scarce, and no previous studies have proposed a similar hypothesis as described here. For this reason, some of the proposals presented here cannot be demonstrated or replicated. Although we inform the individual of their fatigue and discomfort threshold during maximal exercise, we do not present any proposal for measurement. The Borg scale has been employed for decades, connecting individual perceptions to physiological limits during maximal effort competence. Therefore, a separate analysis of the GM and different NTs related to maximal effort tolerance could be proposed for future study. These limitations observed here are the same as those observed in other studies which recently describe the connection between some neuropsychological pathologies, such as depression, anxiety, hyperactivity, and even neurodegenerative diseases. Despite the present limitations, this article could contribute to considering the GM state in states of physical underperformance associated with fatigue or discomfort tolerance.

An appropriate management of tolerance to effort and discomfort during intense endurance exercise is a key factor for successful performance in competition. Higher tolerance for effort and discomfort is certainly an advantage for competitive athletes. In this context, the GM state is physiologically important for the athlete's health, exercise performance, and competition success, which is also associated with improved sensory effort tolerance. Previous studies in other medical areas have suggested that the GM composition can improve pain tolerance during degenerative injuries, such as osteoarthritis, as well as in medical treatments, including chemotherapy or post-surgery states. Concerning endurance performance, only a few data are available on the potential role that certain GM phenotypes could play in increasing the maximal tolerance to effort and fatigue. Here, we hypothesise that GM status may modify cognitive processes of discomfort, pain, and/or effort during intense exercise through the modulation of systemic and local inflammation, gut barrier permeability, vagal signalling, and the production of metabolites and neurotransmitters in the intestines, as well as their direct connection with the brain. Furthermore, we propose specific bacteria that have been described as modulators of different GM metabolites related to the regulation of pain, discomfort, and effort tolerance through the modulation of gut peptides, hormones, and neurotransmitters. The GM is modified through exercise in athletes, but at the same time precision nutrition and probiotics may be optimal for modulating specific perceptual responses and brain sensations. Future studies should evaluate whether perceptions resulting from high-intensity training are necessary to stimulate the GM and the increase in particular bacteria related to the favourable modulation of gut permeability and anti-inflammatory levels. It is reasonable to think that a favourable GM state could improve CNS connections related to effort tolerance, stimulating areas of the brain involved in emotions and perceptions.