Gut Microbiota and Exercise: Probiotics to Modify the Composition and Roles of the Gut Microbiota in the Context of 3P Medicine

Abstract

Prolonged and intense physical activity can trigger stress response mechanisms across various physiological systems—including the cardiovascular, respiratory, gastrointestinal, musculoskeletal, and neuroendocrine systems—disrupting energy metabolism, immune function, redox balance, and hormonal regulation. Critically, when not accompanied by adequate recovery, such exertion may impair rather than enhance athletic performance. In parallel, there has been growing interest in probiotics as natural, safe, and accessible dietary supplements with the potential to support performance and recovery. Emerging evidence highlights the pivotal role of the gut microbiome in mediating communication along the gut–brain and gut–muscle axes, thereby influencing not only metabolic and immune functions but also neuromuscular adaptation and fatigue resistance. This review explores the mechanisms through which probiotics may enhance exercise performance, mitigate exercise-induced fatigue, and improve physiological adaptation via modulation of inflammation, oxidative stress, and metabolic signaling pathways. Framed within the context of predictive, preventive, and personalized medicine (3P medicine), this paper emphasizes the diagnostic and therapeutic potential of personalized probiotic strategies in optimizing athletic performance through the qualitative and quantitative assessment of microbiota and host responses.

Introduction

In 1974, the term “probiotic” was used for the first time and evolved to its definition that is currently used: live microorganisms that can provide beneficial effects for individuals’ health when consumed at reasonable amounts as suggested by the World Health Organization in 2002 [1]. Fungi, bacteria, viruses, and bacteria are all considered microbiomes. Although there are an equal number of bacteria and cells in the human body, the number of genes in the human genome is significantly less compared to the number of genes in the genomes of the microbiome, with a difference of almost 100-fold. The roles of gut microbiota are various and vital, such as digestion, absorption, secretion of necessary vitamins (e.g., vitamin K, folic acid), and protecting the digestive tract [2]. While certain gut microbes are known to synthesize vitamins such as vitamin K and folate, the extent to which these vitamins are bioavailable and absorbed—especially in the case of vitamin B₁₂—remains an area of ongoing investigation, and therefore, their contribution to host vitamin status should be interpreted with caution [3]. Probiotics, which are produced through bacterial fermentation, can be found in a variety of foods including cheese, yogurt, and cultured buttermilk. Furthermore, they can also be found in pickles, beer, bread, olives, sourdough, chocolate, kimchi, sauerkraut, and Japanese miso. Notably, yogurt and fermented milk are still the most common sources of probiotics among the mentioned foods since they create a rather low pH in which these beneficial bacteria can survive. Studies have demonstrated that probiotics can also be obtained from nondairy fermented foods such as cabbage, grains, soy-based products, sorghum, corn, and pearl millet. In addition, probiotics can originate from breast milk, the digestive systems of humans, and the intestinal tract of various other animals, such as rats, poultry, and pigs [4, 5].

The composition of microorganisms that are colonized in the human body is proven not to be accidental. Notably, the term “microbiome” consists of the whole genome of all microorganisms that exist in a specific environment. There are both negative and positive connections between components of the microbiome which affects the health of its host. In addition to interrelationships between components of the microbiome, there are interactions between the microbiome and the cells of the host. Microbiome is spread across various body parts, including skin, mouth, vagina, upper respiratory tract, and ear canal. However, most of these organisms are colonized in small intestines and colon [6, 7]. There have been extensive research efforts into the potential of probiotics to serve as both a preventative and healing tool for a range of different illnesses and health issues, such as cystic fibrosis, irritable bowel syndrome, allergies, lactose intolerance, and infections of the gastrointestinal and urogenital systems [8–15]. Furthermore, probiotics are shown to exert beneficial effects in several cancers of colorectal, breast, bladder, and head and neck [16–20]. Despite the decades of research in the field of probiotics and a vast number of studies, conclusions are still controversial, and definitive decisions, as well as a consensus, remain to be met. In addition, no probiotic formula has been granted approval for medicinal use by regulatory bodies such as the US Food and Drug Administration and the European Food. This issue has led to marketing purposes other than beneficial effects, such as not affecting food taste, viability in the gastrointestinal tract, and safety [21].

Physical exercise is a powerful physiological stimulus that, when appropriately applied, promotes systemic health and performance adaptation. However, its effects on homeostasis are complex and highly dependent on the type, intensity, duration, and recovery status of the exercise [22, 23]. Acute bouts of high-intensity or prolonged physical activity transiently disturb homeostatic balance, activating multiple biological systems including immune, endocrine, metabolic, and neuromuscular networks [24]. This activation is essential for initiating adaptations such as muscle hypertrophy, mitochondrial biogenesis, and improved cardiorespiratory capacity.

A central component of these adaptations is the inflammatory response, which must be carefully regulated [25]. Exercise-induced inflammation is a physiological response involving increased levels of pro-inflammatory cytokines such as IL- 6, tumor necrosis factor α (TNF-α), and IL- 1β, particularly in response to muscle damage or metabolic stress. Importantly, this inflammation is not inherently harmful—rather, it is necessary for triggering tissue repair, immune regulation, and remodeling [26, 27]. However, when recovery is inadequate, or exercise becomes chronic and excessive, this adaptive inflammation can become dysregulated, contributing to oxidative stress, immune suppression, muscle catabolism, and ultimately performance decline or overtraining syndrome [28, 29]. The gut plays a pivotal role in regulating systemic inflammation through its effects on intestinal permeability, microbial composition, and production of immunomodulatory metabolites such as short-chain fatty acids (SCFAs) [30, 31].

Probiotics can help fine-tune this delicate balance. Rather than blunt the acute, necessary inflammation that facilitates adaptation, probiotics may support resolution of inflammation, enhance mucosal immunity, restore microbial diversity, and protect gut barrier function [32, 33]. Thus, in the context of personalized exercise programming, probiotics may offer a targeted approach to managing exercise-induced inflammation, preserving the adaptive benefits while minimizing performance-impairing consequences.

According to the FAO/WHO, the guidelines for probiotics should be utilized as a means of evaluating their potential to promote human well-being, thus furthering their ability to make health statements. The steps that are suggested by this guideline are as follows: (1) identification of a strain, (2) characterization of the strain(s) regarding probiotic properties and safety issues, (3) validation of predicted health benefits by clinical trials, and last but not least, (4) providing honest data without any false claims regarding the efficacy of products [34]. In this article, we delve into the various ways in which the gut microbiome contributes to human well-being, including the connections between the gut and the brain and muscles. Furthermore, we take a look into the studies that investigate the role of probiotics in exercise performance, preventing exercise-induced fatigue, and increasing adaptation. Therefore, in order to achieve better results for both the individual and society at large, the fundamental tenets of 3P medicine—individualized subject profiles and tailored preventative, early predictive, or therapeutic strategies—should be applied in athlete management. In this sense, finding new biomarkers derived from the body—particularly those related to inflammation, oxidative stress, and cognitive function—is necessary for better athlete management. This study explores how probiotics can enhance exercise performance and recovery through gut microbiota modulation, aligning with 3P medicine’s goal of personalized, preventive, and predictive health strategies. This study is necessary to uncover how targeted probiotic interventions can optimize gut–muscle–brain interactions, offering innovative, non-pharmacological strategies for enhancing athletic performance and preventing exercise-related fatigue. In conclusion, identifying the biomarkers of oxidative stress, inflammation, and cognitive decline in athletes is essential to the individualized and preventative strategy of modern medicine.

Gut–Brain Axis and Microbiota

Recent studies have revealed that from early embryonic development, a symbiotic relationship is established between the gut microbiome and the central nervous system (CNS), influencing the cognitive and mental advancement of a newborn [2]. It has been demonstrated through preclinical research that there is a mutual interaction between the brain, gut, and gut microbiome. The interaction between the gut and brain is believed to rely on a range of signal molecules and communication pathways. Clearly, multiple feedback loops are suggested to impact a range of channels [35]. The communication between the CNS and gut takes place through intricate networks of neuroendocrine, neuroimmune, and autonomic pathways, involving both the sympathetic and parasympathetic branches of the enteric nervous system. The sensation of feedback from the intestines to the upper lumbar and thoracic spinal cord, as well as the nucleus of the solitary tract, is controlled by afferent vagal sensory and spinal nerves. By means of these routes, signals that involve multiple synapses activate areas of the brain that are located at a higher level, such as the limbic forebrain and hypothalamus. Furthermore, some areas modify spinal and vagal autonomic response to viscera, such as the hypothalamus, insular cortex, cingulate cortex, red nucleus of the stria terminalis, and amygdala. These structures create projections of preautonomous neurons that lead to bidirectional control over the gut–brain axis. Furthermore, along with the previously mentioned pathways, this axis also involves the activation of humoral and hormonal signaling pathways [36].

Once food has been consumed, the gastrointestinal system produces messages that relay information to the central nervous system regarding the contents and quantity of the meal [37–39]. After receiving these indications, various parts of the brain, specifically the hypothalamus, oversee the control of food consumption, maintenance of stable glucose levels, and the consumption of energy [40, 41]. By sensing the luminal milieu, neuroendocrine cells of the intestines, namely, enteroendocrine cells, release peptides that serve as regulators of glucose homeostasis, including GLP- 1 and cholecystokinin [42]. These gut peptides activate vagal neurons innervating tissues adjacent to intestines in a paracrine manner. Consequently, a signal is sent to the brain. Furthermore, gut peptides may act in an endocrine manner by sending signals to the brain and organs that regulate metabolic homeostasis [43]. Research suggests that the gut microbiota plays a role in regulating energy levels and blood sugar regulation through various pathways such as the gut–brain connection and direct interaction with the brain via microbial byproducts, due to the extensive quantity of microbial cells and genetic material present [44, 45].

While much attention has been given to neuronal and hormonal signaling, the role of the gut microbiota as a central modulator within this axis is increasingly recognized. Microbial metabolites such as SCFAs (e.g., acetate, propionate, and butyrate), secondary bile acids, neurotransmitter-like molecules (e.g., GABA, serotonin, dopamine precursors), and indole derivatives play pivotal roles in influencing mood, cognition, appetite, and stress responses [46, 47]. These metabolites can modulate blood–brain barrier permeability, microglial activation, and neurotransmitter release, impacting both brain function and behavior [48, 49].

Bacterial compounds have the capability to adapt and transform brain processes. This is evident through the release of bacterial molecules in the gut as a reaction to psychological stress, causing shifts in the permeability and movement of the digestive system. Ultimately, this results in adjustments to the gut's conditions and the makeup of its microbiome. The pituitary gland produces adrenocorticotropic hormone in reaction to the release of corticotrophin-releasing factor from the hypothalamus, triggered by external stressors like pro-inflammatory cytokines. This process consequently results in the secretion of cortisol, a stress hormone, which affects multiple organs, such as the brain [50]. Cortisol serves as the regulator of neuroimmune signals which can change the integrity of the intestinal barrier. Furthermore, CNS neurotransmitters, stress hormones, and immunomodulators are capable of altering the gut environment and composition of microbiota by activating neuronal cells of enteric nervous systems and vagus afferent pathways [51].

Notably, SCFAs, tryptophan metabolites, and other bacterial byproducts can reach the CNS via the portal and systemic circulation, modulating neuroinflammation, neurotransmitter biosynthesis, and even behavior. For example, butyrate has been shown to enhance memory and reduce anxiety in animal models, likely through histone deacetylase inhibition and anti-inflammatory effects in the brain [52, 53].

Novel studies have indicated that gram-negative bacteria (most commonly the genus Bacteroides) are able to create extracellular vesicles from their own surface membrane which is called outer membrane vesicles. These vesicles are carriers for enzymes, metabolites, toxins, and nucleic acids and interact with epithelial cells and beyond to reach extra-gastrointestinal areas via two different pathways. Paracellular and transcellular [50] substances produced by microorganisms, including short-chain fatty acids and 4-ethylphenylsulfate, travel through the portal circulation and have an impact on the immune system, metabolism, and nerve cells in the gut's enteric nervous system, as well as on the vagus nerve's afferent fibers [51].

In summary, the microbiota is not a passive player in the gut–brain axis but a dynamic regulator that communicates with the CNS through immune, endocrine, metabolic, and neural signals. Disturbances in microbial balance—whether due to stress, diet, or antibiotics—can disrupt this axis and are implicated in mood disorders, cognitive decline, and altered exercise performance. Therefore, maintaining a healthy gut microbiome through diet, prebiotics, probiotics, and physical activity may offer a novel avenue for supporting mental resilience and optimizing brain function in both clinical and athletic contexts.

Gut–Muscle Axis and Microbiota

Skeletal muscles make up a significant portion of the body, comprising approximately 40–50% of body weight, and are an ideal location to contain protein in the form of amino acids [34]. Throughout the life of an individual, multiple signals are capable of modulating and affecting skeletal muscle, such as growth factors, neural activation, nutritional status, and mechanical loading [54, 55]. By secreting different myokines, skeletal muscles play a role as signaling organs similar to gut microbiota [56]. Indeed, the crosstalk between muscles and other organs (e.g., gastrointestinal system) has led to many questions to be answered and researched [57]. Net protein balance is determined by calculating the disparity between the rates of skeletal muscle protein synthesis and muscle protein breakdown; however, it should be noted that protein balance is a more complex process and cannot be simply reduced to the concept of synthesizing and breaking down proteins [58]. Indeed, several molecules and signal pathways work together as a network to maintain protein balance as a crucial process for the mass and function of muscles [59].

As stated earlier, the microbiomes found in the digestive system have a significant impact on both the maturation and functioning of the central nervous system. However, microbiota roles are not limited to CNS functions and they also affect appetite and homeostasis of energy. Furthermore, microbiota modulates the metabolism of skeletal muscles by metabolites (e.g., BAs and SCFAs), leading to the regulation of animal energy homeostasis. SCFAs trigger the activation of AMPK through the process of phosphorylation within both myotubes and skeletal muscles. This provides a higher concentration of AMP and AMP/ATP [60]. Furthermore, the downstream effects of phosphorylated AMPK include the activation of p38MAPK and peroxisome proliferator-activated receptor γ coactivator- 1-α (PGC- 1α) [61]. Biosynthesis of mitochondria, improved mitochondria function, and fatty acids’ oxidative metabolism are some of PGC- 1α's roles [62]. The activation of AMPK also leads to the liberation of HDAC5 through a rise in the abundance of the glucose transporter, GLUT4, and the phosphorylation of HDAC5 within the primary myotubes'nucleus [63]. Through the facilitation of GLUT4, glucose is able to enter the muscle cells, resulting in a significant boost in the accumulation of muscle glycogen [64]. SCFAs have the ability to attach to both GPR41 and GPR43 receptors, stimulating the L cells found in the colon and pancreas tissue. This results in the production of two important hormones, GLP- 1 and insulin [65]. PI3 K is activated and protein levels of GLUT4 in the cytoplasm are enhanced by GLP- 1 signaling via GLP- 1 receptor. This leads to enhanced absorption of glucose by cells. Moreover, GLP- 1 increases the uptake of glucose without dependence on PKB phosphorylation while increasing glucose storage without dependence on GSK3 phosphorylation [66]. Thus, it is indicated that GLP- 1 enhances the uptake and metabolism of glucose while increasing the synthesis of glycogen and aggregation of microvessels in skeletal muscles [67]. Through increasing glucose transport and fructokinase 6-phosphate, a hexokinase, insulin enhances glycolysis [68]. Meanwhile, the expression of ACC, FAS, and SREBP- 1, lipogenesis genes, are suppressed by the enhanced activity of AMPK [69]. Furthermore, AMPK increases the catabolism of lipids while decreasing fat accumulation in muscles through increasing the expression of HSL, LPL, CPT1, and U genes. In contrast, the production of bile acids by gut bacteria can function as signaling molecules to regulate G protein–coupled bile acid receptor 1 (TGR5) and augment energy metabolism in muscles, while also promoting the stimulation of thyroid hormone [70]. By triggering the nuclear FXR, bile acids can reduce the accumulation of fat. Hence, the gut microbiota has the ability to produce substances that aid in regulating glucose levels and promoting muscle fat metabolism [71].

Preclinical studies using germ-free or antibiotic-treated animals have demonstrated impaired muscle mass, mitochondrial function, and endurance capacity, which are restored upon colonization with healthy microbiota or supplementation with specific probiotics such as Lactobacillus plantarum TWK10 and Bifidobacterium longum OLP- 01 [72–75]. These strains not only reshape gut composition but also influence fatigue resistance, glucose homeostasis, and antioxidant capacity in muscle.

Therefore, the gut–muscle axis is not simply a byproduct of host metabolism, but rather a dynamic, microbiota-modulated system. Exercise, in turn, alters microbiota composition—often increasing SCFA-producing species—creating a positive feedback loop that supports muscle adaptation and systemic homeostasis. Understanding this bidirectional interaction opens new possibilities for microbiome-based strategies to enhance muscle health, athletic performance, and metabolic resilience.

Probiotics'Effects on Exercise Performance

Numerous research studies have thoroughly examined the impact of probiotics on improving physical performance and alleviating fatigue caused by exercise [32, 33, 76, 77]. An investigation was done on athletes who participate in mixed martial arts (MMA) through a double-blind randomized trial. This study examined the impacts of vitamin D₃, probiotics, and a combination of the two on specific indicators of exercise performance. In comparison to the group that only received vitamin D, the group that received both vitamin D and probiotics displayed reduced levels of lactate 1 h after the acute sprint interval. In addition, it can be stated that solely the team that was administered the combined treatment demonstrated a rise in overall workload and average strength following the anaerobic workout regimen. The ratio of T60/T3 in the combined therapy group was significantly higher compared to the vitamin D group, with values of 73.6 ± 6.9% and 65.1 ± 9.9%, respectively, indicating an increase in lactate use. In other words, the correlation can be made that the use of both vitamin D and probiotic supplementation results in an enhanced anaerobic performance for MMA athletes [78].

Lactobacillus Plantarum

A comprehensive analysis was conducted on the effects of Lactobacillus plantarum TWK10 (TWK10) on performance, body composition, and exercise adaptation in a group of 54 healthy participants aged 20–30 years old, who were not professional athletes. The study was conducted in a double-blind manner, and various parameters such as lactic acid, blood ammonia, blood glucose, and creatinine kinase were measured. The results demonstrated that TWK10 has a considerable impact on improving an individual's exercise performance, and this effect is directly proportional to the dosage used. Moreover, the supplement was found to enhance various aspects that contribute to physical fatigue. Hence, this process results in enhanced physiological adjustment. Additionally, the participants who consumed TWK10, especially in large amounts, experienced a notable increase in muscle mass and a significant decrease in body fat [79]. Chen and colleagues conducted a study in which they fed mice of the Male Institute of Cancer Research (ICR) strain L. plantarum TWK10 (LP10) for a continuous period of 6 weeks. This was done to observe the impact of LP10 on the gut microbiome, exercise performance, and physical fatigue [80]. Based on findings, it has been noted that LP10 has a significant impact on enhancing grip strength, lengthening the time for endurance swimming, and increasing overall muscle weight. Meanwhile, it reduced final body weight, serum lactate, ammonia, creatine kinase, blood urea nitrogen (BUN), creatinine, albumin, triacylglycerol, and glucose. Following administration of LP10, the number of slow muscle components, type 1 fibers, has been significantly increased in gastrocnemius muscle [80]. Lee and colleagues have reported that in young mice, TWK10 increases muscle strength, while in aged mice, it reduces the age-related muscle strength loss. Also, TWK10 supplementation has been shown to prevent aging-related reduction in bone mass, learning, and memory functions. According to the results of next-generation sequencing (NGS) analysis of the 16S rRNA gene, a period of 8 weeks of taking TWK10 supplements causes noticeable alterations in the makeup of gut bacteria. Without a doubt, the inclusion of TWK10 in mice's diet resulted in a significant rise in bacteria that produce SCFAs and a considerable overall increase in the levels of SCFAs in the gut. Significantly, this addition also reduced the buildup of harmful bacterial groups that are linked to the aging process [81]. Aside from research on animals examining the impact of TWK10 on physical performance and associated factors, Huang et al. also delved into this topic [82] and have performed a study on the role of TWK10 on endurance performance in humans. Supplementing adult subjects over 20 years old with TWK10 for 6 weeks has led to increased levels of creatine kinase, lactic acid, blood glucose, ammonia, and free fatty acids following exhaustive exercise. After receiving TWK10 supplementation, individuals displayed higher levels of endurance and glucose content during a maximal treadmill running test when compared to those in the control group. Thus, it is recommended that this addition may prove beneficial in increasing energy acquisition [82]. A new experiment was conducted on a group of older individuals with slight frailty in order to thoroughly evaluate the impact of TWK10 on both muscle mass and functional ability. The findings of the study showed that administering TWK10 for a duration of 6 weeks resulted in a significant growth in muscle mass and an improvement in left hand grip strength. However, it was also observed that there was a decrease in limb muscle strength, balance, and gait speed after the allotted time period. Supplementing individuals for longer periods of time up to 18 weeks caused more significant impacts. In summary, it can be inferred that providing TWK10 supplements for a duration longer than 6 weeks can enhance the muscular strength and endurance of older individuals, as well as reduce susceptibility to physical weakness and decreased muscle mass [83].

A recent research has been conducted on the impact of Lactobacillus plantarum (PL- 02) on muscle growth, physical performance, and fatigue during exercise using mice as subjects. In this research, it is demonstrated that the utilization of PL- 02 over a period of 4 weeks leads to enhancements in muscle mass, endurance, and muscle mass, as well as increases in glycogen storage in both muscle and liver tissues. Moreover, after undergoing PL- 02 treatment, the levels of BUN, creatine kinase (CK), and ammonia are known to decrease. This leads to the conclusion that PL- 02 has the ability to effectively combat fatigue [84]. A separate research undertaking looked into the impact of combining PL- 02 with resistance training on both muscle mass and physical performance during exercise. The findings showed that when PL- 02 was given for a duration of 4 weeks along with resistance training, there was a noteworthy rise in the total number of crawls, time taken for full exertion during exercise, and the strength of gripping. In comparison, it decreases lactate, ammonia, creatine kinase, BUN, and the time required for a single climb. It is also suggested that this supplementation provides increased muscle mass without leading to physical damage [85]. Lee and colleagues have investigated the benefits of Lactiplantibacillus plantarum “Tana” in exercise performance. The findings showed that when mice were given Tana supplementation for a period of 4 weeks, their endurance and grip strength improved, and there was also an increase in glycogen storage in both the liver and muscles. As evidenced by decreased levels of CK, lactate, BUN, and ammonia, Tana also exerts anti-fatigue effects dose-dependently [86].

A study was conducted to examine the impact of Lactobacillus plantarum KSFY01 on the exercise capacity of mice experiencing an accelerated aging state induced by oxidative stress. Based on the findings, there was a noticeable increase in the running duration of mice after the oral administration of L. plantarum KSFY01. Additionally, the levels of ALT, AST, BUN, lactic acid, lactate dehydrogenase, and CK are notably reduced. Furthermore, the consumption of L. plantarum KSFY01 boosts mice’s ability to perform physical activity, ameliorates liver injury, and relieves tiredness caused by exercise. In a living organism, examinations showed that L. plantarum KSFY01 boosts the effectiveness of antioxidant enzymes, maintains a healthy balance between pro-oxidative and anti-oxidative substances, and lowers the quantities of malondialdehyde (MDA). Moreover, this supplement shows a significant correlation with increasing levels of antioxidant function by countering the decrease in factors associated with nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling in a dose-dependent manner [87]. A study was carried out on mice from the ICR to examine the effects of exercise-induced exhaustion and treatment with Lactobacillus plantarum CQPC02 for a period of more than 4 weeks on fatigue levels and biochemical oxidation processes [88]. In experiments, both vitamin C and LP-CQPC02 demonstrated the ability to significantly extend the time a subject could swim before experiencing exhaustion, with vitamin C acting as the designated positive control. According to reports, an increase in LP-CQPC02 concentration is directly linked to an extended exhaustion time. After undergoing LP-CQPC02 treatment, levels of liver glycogen, free fatty acids, and skeletal muscle glycogen show a significant increase. Conversely, levels of BUN and lactic acid experience a decrease. The drug known as LP-CQPC02 has a dose-dependent effect on lowering MDA levels, as well as simultaneously increasing levels of catalase (CAT) and superoxide dismutase (SOD). In the mouse model for liver tissue exhaustion caused by swimming, it has been observed that LP-CQPC02 increases the levels of messenger RNA for copper/zinc-superoxide dismutase, manganese-superoxide dismutase, and catalase. In addition, the gene expression of alanine/serine/cysteine/threonine transporter 1 (ASCT1) is increased due to the administration of LP-CQPC02, whereas the levels of TNF-α, syncytin- 1, and inducible nitric oxide synthase (iNOS) are decreased in the skeletal muscle of mice in a state of exhaustion caused by swimming [88]. For a period of 4 weeks, a group of athletes who underwent rigorous triathlon training incorporated Lactobacillus plantarum PS128 into their routine. This was done to study the effects of the supplement on their physical adaptability and overall performance during exercise [89]. The findings showed that participants who received PS128 experienced a significant increase in endurance, with a 130% difference compared to those in the placebo group. However, there was no difference between the treatment and placebo groups regarding the maximal oxygen consumption and composition. PS128 is shown to significantly decrease Oxalobacter, Anaerotruncus, Holdemania, Caproiciproducens, Family_XIII, Coprobacillus, Dielma, and Desulfovibrio while increasing Lactobacillus, Akkermansia, Butyricimonas, and Bifidobacterium. Moreover, the group that received supplementation showed less diversity compared to the placebo group. The group that received supplements were found to have substantially elevated levels of SCFAs, specifically butyrate, acetate, and propionate. In summary, the suggestion is that this supplementation enhances stamina for running through the regulation of microbiota [89]. A separate research also indicated that the use of PS128 in conjunction with physical activity positively impacts markers of oxidative stress, such as myeloperoxidase, creatine kinase, and thioredoxin following participation in a triathlon. Following physical activity, there is a significant reduction of 6–13% in pro-inflammatory cytokines such as IL- 6, IL- 8, and TNF-α, while there is a notable increase of 55% in anti-inflammatory markers like IL- 10. In addition, the levels of plasma-branched amino acids substantially rise between 24 and 69% after the administration of PS128 [90]. A study was conducted using a double-blind, randomized, crossover design to examine the effects of ingesting two capsules (each containing 3 × 10¹⁰ CFU) of PS128 on exercise performance and physiological changes after completing a half-marathon. Despite the fact that both the treatment and placebo groups completed the half-marathon in the same amount of time, the treatment group is noted to have a higher proportion of participants reaching stage 4 of the race. The placebo group had lower measurements for strength in their lower limb muscles, as determined by an isokinetic dynamometer, 72 h after exercising when compared to the treatment group. In addition, the participants who received the placebo experienced a significant decrease in lower limb explosive force during the countermovement jump test after 24 h.

Based on the findings, it has been observed that individuals in the treatment group experienced decreased levels of creatine phosphokinase and myoglobin, which are markers for muscle damage, following their participation in a half-marathon. In addition, the group receiving treatment showed a significant increase in superoxide dismutase levels and a successful recovery of BUN levels within 24 h [91]. Yu and his team conducted extensive research on the influence of PS128 in the areas of muscle fatigue and electromyography, specifically focused on median power frequency (MDF), integrated electromyography (iEMG), and neuromuscular efficiency (peak torque/iEMG) following a half-marathon race. The placebo group experienced a decrease in maximal voluntary isometric contraction of the knee extensors at various time points, including 48 h before the half-marathon and 0, 3, 24, 48, 72, and 96 h after. Moreover, the group receiving the placebo exhibited a notable decline in the MDF (mean frequency) of the vastus medialis oblique muscle 24 h following the half-marathon. The iEMG of the vastus medialis oblique was also significantly decreased in the placebo group 48 h after the half-marathon. Significantly, the initial electromyographic activity (iEMG) and mean frequency (MDF) of the placebo group were found to be consistently lower than those of the treatment group at a variety of time points following the half-marathon, including 0, 3, 24, 48, and 72 h. These findings suggest that incorporating PS128 supplementation may have the potential to inhibit the decline of iEMG, peak torque, and MDF after engaging in physical activity [92].

Lactobacillus Paracasei

An investigation on Lactobacillus paracasei for increasing the rate of recovery and decreasing exercise-induced muscle damage has been done. It is observed that supplementations of both heat-killed L. paracasei and live L. paracasei are capable of slowing injury-induced loss of muscle strength. Also, they can significantly decrease the production of inflammatory and damage-induced markers. These supplementations are also found to increase muscle strength and recovery while slowing testosterone level decline. Altogether, it is concluded that administration of L-PS23 or HK-PS23 for 6 weeks improves inflammatory and blood muscle damage markers, slows damage-induced strength loss, and fastens muscle recovery [93]. Bjerg et al. have studied the role of Lactobacillus paracasei subsp. paracasei L. casei W8 (L. casei W8) on the responses of glucagon-like peptide- 1 (GLP- 1) in piglets, isolated pig intestine, and humans. In piglets, administrating L. casei W8 for 2 weeks causes higher expression levels of glucagon encoding gene (GCG) compared to the control group. In isolated pig intestine, L. casei W8 supplementation leads to higher GLP- 1 responses, and in humans, the supplementation makes an effect on energy intake without affecting appetite, glucose and insulin response, and GLP- 1 release. Therefore, it is concluded that L. casei W8 supplementation can serve as an agent that lowers food intake [94].

Lee et al. investigated the role of L. paracasei PS23 on muscle damage after exercise. Three groups including placebo, live, and heat-killed L. paracasei PS23 (supplemented for 6 weeks) were included in this study. Results revealed significant muscle mass improvement and reduction of loss of strength in the both intervention group. Accelerated recovery, reduction of inflammatory biomarkers, and improvement of blood muscle damages are other beneficial effects which were seen in the intervention groups especially in the heat-killed group [95].

Lactobacillus Fermentum

Liu et al. have studied the role of Lactobacillus fermentum CQPC08 (CQPC08) in attenuating exercise-induced muscle fatigue by exerting antioxidative effects and intervention of galactooligosaccharide in mice. As CQPC08 combined with GOS decreases oxidative damage in liver that is induced by fatigue, it is able to reduce different related factors, including IL- 1β, IL- 6, BUN, glutamic-pyruvic transaminase, lactic acid, TNF-α, glutamic-oxaloacetic transaminase, inducible nitric oxide synthase (iNOS), and malonaldehyde (MDA). Meanwhile, serum levels of SOD, CAT, and glutathione peroxidase are reported to be elevated. Moreover, treating mice with CQPC08 and GOS results in reduced expression of TNF-α, neuronal NOS (nNOS), and iNOS while increasing expression of manganese (Mn) and copper/zinc (Cu/Zn) SOD at mRNA level in both liver and muscles [96].

Lee et al. have studied the role of Lactobacillus rhamnosus JY02 in preventing and alleviating sarcopenia. In C2 C12 cells, L. rhamnosus JY02 is reported to decrease markers of muscle degradation, such as atrogin- 1 and MuRF1. Moreover, it reduces myotube diameter atrophy that is induced by dexamethasone. In addition, it is observed that administration of L. rhamnosus JY02 results in an increase in markers that improve muscles, such as Myo-D, MHC Iβ, and MHC Iiα. In comparison, it decreases markers of muscle degradation as well as symptoms suggesting muscle atrophy, including loss of muscle strength and lean mass. L. rhamnosus JY02 increase anti-inflammatory factors, such as IL- 10, while reducing pro-inflammatory markers, such IL- 6, and IFN-γ. Therefore, it is suggested that this supplementation can be used as an anti-sarcopenia agent by decreasing muscle atrophy [97].

A study investigated the effects of 4-week Lactobacillus fermentum (LF) HFY03 gavage on running exhausted mice. They demonstrated that both vitamic C, as positive control, and LF-HFY03 are capable of significantly enhancing the running time. The concentration of LF-HFY03 is reported to be positively correlated with the extended exhaustion time. Following treatment with LF-HFY03, levels of BUN and lactic acid were lowered while levels of liver glycogen and free fatty acid contents were increased. Furthermore, AST, ALT, and CK levels gradually reduced in mice concurrently as the increase in antioxidant peptide level of walnut albumin. In addition, CAT and SOD levels are increased by LF-HFY03 administration and MDA levels are decreased. In the mice liver, Cu/Zn-SOD and Mn-SOD as well as CAT mRNA levels are increased by LF-HFY03. However, the expression of threonine transporter 1 (AST1)/alanine/cysteine/serine, nNOS, and eNOS are increased. Thus, it is concluded that LF-HFY03 can act against fatigue [98]. A study has been conducted on 20 healthy elite male distance runners who received a daily dose (1.26 × 10¹⁰) of Lactobacillus fermentum VRI- 003. Results showed that athletes experienced fewer days with respiratory symptoms compared to placebo group (30 vs 72 days). In addition, illness severity is also reported to be lower in individuals who were treated with VRI- 003. While there was no difference in the mean changes of IL- 4, IL- 12, salivary IgA, and IgA1 levels, the group who received supplement showed higher alteration in whole-blood culture interferon gamma (IFNgamma). Notably, no changes have been observed in running performance during the study period. Thus, it is concluded that VRI- 003 supplement is correlated with a reduction in respiratory illness severity and duration [99].

Lactobacillus Salivarius

An investigation has been conducted on the role of gut microbiome isolates from the 2008 Olympic women's 48-kg weightlifting gold medalist's gut microbiota, Lactobacillus salivarius subsp. salicinius (SA- 03), on physical health of male mice. The findings have shown that supplementing mice with 4 weeks of this probiotic leads to increased endurance and muscle strength as well as glycogen storage of muscles and liver. Furthermore, it reduces BUN, CK, ammonia, and lactate [100].

Veillonella Atypica FB0054

In an investigation by Scheiman et al. [101], it is observed that Veillonella relative population is increased in marathon runners after marathon. Also, a strain of Veillonella atypica is isolated from their stool samples retrieved from tubes placed in the soild toilet tissue. Following inoculation of this strain, exhaustive treadmill run time of mice has been significantly increased. Lactate is the only carbon source of Veillonella and as it is demonstrated in this study, genes of lactate metabolizing pathway to propionate are higher after exercise. Interestingly, intrarectal instillation of propionate leads to an increase in treadmill run time which also occurs following the gavage of V. atypica [101].

However, it is important to interpret these findings within the context of extreme physical stress. Marathon runners often experience nutritional depletion, sleep disruption, increased gut permeability, and systemic inflammation, all of which can transiently shift microbiota composition. Thus, the observed bloom of Veillonella may represent a reactive microbiome adaptation to elevated systemic lactate and immune stress, rather than a stable feature associated with enhanced performance in broader athletic populations.

A study on seven healthy individuals who were treated with 1 × 10¹⁰ CFU doses of the probiotic Veillonella atypica FB0054 for 14 days showed that there was no difference in exhaustion times of individuals who received placebo or supplementation. Meanwhile, anoaerobic capacity is reported to be lower in the placebo group. Furthermore, there was no alteration in levels of lactate, bacterial population, or hemodynamics. However, the group that received Veillonella atypica FB0054 showed different expression patterns for 14 metabolites. Altogether, it is concluded that this supplementation prevents the decline in exercise performance which is seen in placebo group [102].

Taken together, Veillonella atypica may play a role in buffering performance decline under intense physiological stress, but evidence for its performance-enhancing effects in typical training conditions remains limited. Further research is needed to clarify whether this genus has therapeutic or adaptive relevance outside of extreme endurance events, and whether its effects are strain, dose, or context dependent.

Bifidobacterium

A study performed on ICR mice investigated the role of Bifidobacterium longum subsp. longum OLP- 01 (OLP- 01) on exercise performance, associated metabolites, and physiological adaptation to exercise. The results showed that treating mice with OLP- 01 for 6 weeks leads to enhanced endurance, grip strength, and fatigue-related factors, such as glycogen content, lactate, lactate dehydrogenase (LDH), ammonia, and creatine kinase. Furthermore, it improves inflammatory and injury-associated factors that are induced by prolonged endurance exercise test, including CK, platelet/lymphocyte ratio, and aminotransferase (AST). Compared to groups who received OLP- 01 and were sedentary, the group who received OLP- 01 and exercised showed higher levels of butyrate, acetate, and propionate [103]. A study conducted on middle- and long-distance runners who received supplementation of Bifidobacterium longum subsp. longum Olympic No. 1 (OLP- 01) combined with regular exercise. Findings revealed that the abundance of gut microbiota and the 12-min Cooper's test running distance have been increased. However, no changes have been observed in body composition of participants. Importantly, no adverse reactions have been reported following OLP- 01 supplementation [104].

In female taekwondo athletes, Zhu et al. have investigated the role of probiotic yogurt supplement in exercise-associated psychological fatigue. They found that 8-week administration of Bifidobacterium animalis subsp. lactis BB- 12 supplementation results in an increase in Athlete Burnout Questionnaire scores. Furthermore, it is observed that there are more populations of Bifidobacterium, Bacteroides, Lachnospiraceae, family _Lactobacillaceae, and genus _Lactobacillus in the dietary intervention group (DK) than in the control group. In comparison, Escherichia coli were lower in the DK group. Biosynthesis of l-arginine via l-ornithine as well as biosynthesis and oxidation of fatty acid have been higher in the CK group. In addition, l-isoleucine biosynthesis III pathways were higher in the CK group. On the other hand, degradation of tyrosine through 2,3-dihydroxyphenylpropionate was lower in the DK group (Table 1) [105].

Table 1.

Studies investigating the effects of Bifidobacterium strain on exercise performance and related factors

Type of probiotic	Subject(s)	Dose	Duration	Findings	Ref
OLP- 01a	ICRa mice	1.03 × 1010 CFU/kg	6 weeks	The exercise + OLP- 01 group showed higher endurance and grip strength, as well as improved fatigue-associated indexes (lactate, ammonia, CK, LDH,a and glycogen content), compared with the other groups	[103]
OLP- 01	C57BL/6 J db/db male mice	1.03 × 1010 CFU/kg/day	6 weeks	The exercise + OLP- 01 group showed higher grip strength and exhaustive swimming time while glycolipid parameters (FBS and HA1c), liver injury parameters (AST, ALT), and pancreas damage were reduced	[137]
OLP- 01	Middle- and long-distance runners	1.5 × 1010 CFU/day	5 weeks	Probiotic enhances the change in the 12-min Cooper's test running distance and the abundance of gut microbiota	[104]
OLP- 01	ICR mice	1.03 × 1010 CFU/kg	5 weeks	Probiotic + exercise training can be helpful treating obesity	[138]
OLP- 01	Male ICR mice	2.05 × 109, 4.10 × 109, and 1.03 × 1010 CFU/kg/day	4 weeks	Probiotic improved performance while reducing fatigue	[139]
Bifidobacterium animalis ssp. lactis BB- 12	Female taekwondo athletes	–	8 weeks	Probiotic increases the clearance of exercise-related psychological fatigue by modulating gut microbiota	[105]
Bifidobacterium animalis subsp. lactis BB- 12	Chongqing young divers	1 × 109 CFU/100 g	8 weeks	Probiotic improves the anxiety of athletes and enhances their performance	(140)
Bifidobacterium lactis BL- 99	Cross-country skiers	1 × 109 CFU	8 weeks	Probiotic enhances lipid metabolism and sports performance by increasing the synthesis of short-chain fatty acids and unsaturated fatty acids	(141)
Bifidobacterium longum 35624	Female swimmers	1 × 109 CFU	6 weeks	Probiotic did not change exercise performance or immune function but changed cognitive outlook	(142)

^aBifidobacterium longum subsp. longum OLP- 01

^aInstitute of Cancer Research

^aLactate dehydrogenase

Indirect Effects of Probiotics on Exercise Performance of Athletes

Moderate exercise training is shown to positively affect the immune system; meanwhile, prolonged intense exercise training has been correlated with a transient decrease in immune system of athletes [106]. Because of the changes that occur in immune system of athletes, individuals may be exposed to higher risk of upper respiratory tract infections (URTIs) [107, 108]. As evidenced by a study, almost 7% of athletes experience one or more episodes of illness during major competitions which take 2 to 3 weeks. About 50% of these illnesses are observed to be respiratory [109]. Multiple mechanisms have been suggested as causes of this issue. For instance, reports have revealed that IgA concentration in saliva is associated with infection episodes [110–112]. Besides, T-lymphocyte distributions of type 1/type 2 are observed to be altered by intense exercise training [113].

Gleeson et al. [114] have conducted a study on the effects of 4-month supplementation with Lactobacillus salivarius in individuals who practiced endurance-based exercises and investigated the association between probiotic administration and occurrence of URTIs and mucosal immune markers. The number of individuals who showed 1 or more weeks of URTI symptoms was the same between the group who received supplementation and those who took placebo (58 vs 59). Besides, both groups showed similar number of episodes for URTI symptoms. Duration of symptoms and severity of the diseases were also not significantly different between two groups. The counts of blood cells (e.g., monocytes, lymphocytes, and neutrophils), lysozyme, and saliva IgA levels were also the same between placebo and treatment group. Therefore, it is suggested that administration of L. salivarius is not useful in decreasing the URTI in athletes [114]. Contrary to the findings of this study, another study has investigated the effects of probiotic supplementation on the URTI symptoms of individuals who also trained endurance-based exercises. It is found that individuals in the placebo group who had 1 or more weeks of URTI symptoms were 36% higher than participants who received Lactobacillus casei Shirota (LcS) as their probiotic supplementation. Episodes of URTI have been also found to be more in the placebo group compared to the treatment group. However, symptom duration and disease severity are reported to be the same in both groups. At baseline, levels of saliva IgA have been observed to be similar in both groups. In comparison, the treatment group revealed to have higher concentration after 8 and 16 weeks of probiotic administration compared to the placebo group. Therefore, it is implied that administration of probiotics as supplementation in athletes may be helpful in decreasing URTI [115].

Nausea, cramping, gastric pain, and diarrhea are some the gastrointestinal symptoms that are induced by exercise and commonly observed in runners participating in competitions [116]. It is estimated that 30 to 90% of athletes experience these gastrointestinal symptoms. Besides, these symptoms are reported to be affective on the performance of athletes and may even lead to their drop-out of the competition [116, 117]. Exactly what mechanism leads to changes in the digestive system after exercise is not known [116]. However, some studies have claimed that the reason behind these changes is the hypoperfusion [118, 119]. Indeed, exercise-induced splanchnic hypoperfusion results in ischemia on the intestine, leading to the damages of epithelial cells. Subsequently, the function of the intestinal barrier is compromised and intestinal permeability is increased [120–126]. For instance, as Karhu et al. found, 90 min of running at a challenging pace causes an increase in permeability of gastrointestinal tract without having any connection with the development of gastrointestinal symptoms [127].

A study has investigated the role of UCC18, a strain of probiotics, in affecting exercise-induced gastrointestinal permeability in healthy individuals. Findings showed that exercise significantly increases the intestinal permeability to sucrose, lactulose, and rhamnose. Meanwhile, UCC118 is found to decrease sucrose permeability without changing the permeability of lactulose or rhamnose. Further assessments demonstrated that following UCC118 administration, 99 bacteria had been modulated differently. Thus, it is concluded that 4 weeks of UCC118 administration can reverse exercise-induced hyperpermeability in the gastrointestinal tract [128]. Another study has been conducted on the effect of 4-week supplementation with multi-strain probiotics on gastrointestinal permeability in male runners. These probiotics which included Lactobacillus, Bifidobacterium, and Streptococcus strains were able to enhance run time to fatigue. They also reduced the concentration of serum lipopolysaccharide both pre- and post-exercise. Moreover, probiotic administration has led to a small decrease in gastrointestinal symptoms of athletes while reducing lactulose/rhamnose ratio of urine [127]. Pugh and colleagues also investigated the changes in gastrointestinal symptoms and permeability following supplementation with probiotics. In a group that took probiotics [Lactobacillus acidophilus (CUL60 and CUL21), Bifidobacterium bifidum (CUL20), and Bifidobacterium animalis subsp. lactis (CUL34)], lower prevalence of moderate gastrointestinal discomfort has been reported during the third and fourth weeks of administration compared to the first and second weeks. In addition, runners who received supplementation showed significantly lower severity in their symptoms during the final third marathon compared to placebo group [129].

Strength, Limitations, and Future Directions

Strength

One of the key strengths of the current body of research on probiotics and exercise performance is the diversity and depth of experimental approaches. Studies have employed both animal models and human trials, including double-blind, randomized, placebo-controlled designs, which are considered the gold standard in clinical research. These robust methodologies help strengthen the validity of findings by minimizing bias and ensuring reliability [130–132].

Moreover, research has gone beyond simply measuring endurance or strength, incorporating biochemical markers such as lactate, CK, BUN, ammonia, cytokines, and oxidative stress indicators. This biochemical profiling enables a more comprehensive understanding of the physiological mechanisms underlying the observed benefits, such as reduced inflammation, improved antioxidant capacity, and enhanced energy metabolism. The inclusion of multi-omics tools, such as NGS of gut microbiota and metabolomic profiling, also adds significant scientific value and mechanistic insight.

Another strength lies in the diversity of probiotic strains studied, including Lactobacillus plantarum, L. paracasei, L. fermentum, L. salivarius, Veillonella atypica, and Bifidobacterium longum. This diversity allows for comparative analysis and highlights that the beneficial effects of probiotics are strain specific and context dependent. Furthermore, many studies also report dose–response relationships, particularly for L. plantarum TWK10, offering important practical guidance for future clinical use [133–136].

A further notable advantage is the translational potential of these findings. Probiotic supplementation is a non-invasive, accessible, and generally safe intervention that can be applied across diverse athletic populations and age groups. The demonstrated improvements in fatigue resistance, muscle strength, immune modulation, and gut barrier function underscore probiotics as a promising adjunct in sports nutrition and preventive health for athletes.

Limitations

Despite the promising findings, several limitations must be acknowledged. First, a large proportion of evidence still comes from preclinical animal studies, which, while informative, may not fully replicate human physiological complexity. Even within human studies, sample sizes tend to be small, often ranging from 10 to 50 participants, which reduces the statistical power and generalizability of the results.

Another major limitation is the heterogeneity of methodologies across studies. Different research groups use varied exercise models, training regimens, participant characteristics (age, sex, fitness level), dosages, and probiotic formulations, making direct comparisons difficult. For instance, studies differ in their probiotic delivery vehicles (capsules, yogurt, etc.), administration periods (4–18 weeks), and strain combinations. This variation can lead to inconsistencies and limits the ability to establish unified, evidence-based guidelines.

Moreover, while some studies report improvements in performance metrics such as endurance and grip strength, others do not find significant differences in VO₂ max, body composition, or performance time. This variability in endpoints makes it difficult to draw definitive conclusions on the ergogenic effects of probiotics.

Another limitation is the short duration of most trials. While several studies have evaluated probiotic use for 4 to 6 weeks, few have extended supplementation over several months or more, which may be necessary to observe long-term effects, particularly in elite athletes or aging populations. The potential for tolerance development, microbiota adaptation, or strain-specific colonization limits over time is also underexplored.

Furthermore, many studies fail to assess participants’ baseline gut microbiota profiles, diet, or genetic background—factors that could significantly influence probiotic effectiveness. Without such personalization, results may not be applicable across broader or more diverse populations. While 3P medicine emphasizes tailored interventions, much of the existing research still relies on one-size-fits-all approaches.

Lastly, regulatory issues remain a challenge. Despite evidence supporting probiotic efficacy in enhancing athletic performance or recovery, no probiotic formulations have yet been approved by the FDA or EMA as medical products for such indications. This lack of regulatory endorsement reflects the need for higher-quality, more standardized clinical evidence.

Future Directions

To overcome current limitations and fully unlock the potential of probiotics in exercise physiology, several research directions should be pursued. First, large-scale, multicenter clinical trials with standardized protocols are necessary to confirm the reproducibility of findings and provide more generalizable data. Such trials should include diverse athletic populations with varying levels of training, age groups, and sex to explore differential responses.

There is also a need for strain-specific research to better understand the unique properties of each probiotic. Given the observed differences in outcomes between strains like TWK10, PS128, and KSFY01, future studies should aim to identify the most effective strains for specific performance goals (e.g., endurance, strength, recovery, or immune resilience). In this context, comparative studies and head-to-head trials of different probiotics would be valuable.

In line with the principles of 3P medicine, future research should incorporate individualized approaches, such as profiling the gut microbiome and systemic biomarkers prior to supplementation. This would enable personalized recommendations based on microbiota composition, genetic polymorphisms, inflammatory status, or oxidative stress markers. Technologies like metagenomics, metabolomics, and machine learning could be used to predict responders versus non-responders and optimize strain selection.

In addition to direct performance metrics, more studies should explore neurocognitive outcomes, such as focus, reaction time, and mood, particularly under exercise-induced stress. Given the emerging evidence on the gut–brain–muscle axis, the impact of probiotics on central fatigue, motivation, and cognitive resilience should be better elucidated.

The long-term safety and sustainability of chronic probiotic use in athletes should also be examined. Future trials should monitor not only benefits but also potential risks, such as microbiome imbalance, over-colonization, or antibiotic resistance gene transfer.

From a practical standpoint, future work should investigate optimal dosing regimens, delivery systems (e.g., encapsulation, functional foods), and co-supplementation strategies. Combining probiotics with prebiotics (synbiotics), polyphenols, vitamins, or amino acids may yield synergistic effects and should be systematically tested.

Finally, efforts should be made to bridge the gap between scientific findings and regulatory acceptance. Building standardized frameworks for probiotic testing and claims validation, aligned with WHO/FAO guidelines, could pave the way for more formal approval and integration into clinical sports medicine practice.

Concluding Remarks and 3PM-Related Outlook

This article contributes to the growing body of evidence on the role of specific probiotic strains in enhancing exercise performance, reducing fatigue, modulating inflammation, and improving gut–muscle–brain axis function through both direct and indirect mechanisms. The authors should critically assess their findings by identifying patterns across studies (e.g., strain-specific benefits like TWK10’s effects on muscle mass or PS128’s anti-inflammatory impact), discussing inconsistencies or null results, and evaluating how these outcomes support or challenge existing theories. A comparative synthesis and a reflection on the translational value and limitations of current data would strengthen the manuscript’s scientific contribution.

A great number of investigations have shown that gut microbiota plays a pivotal role in human health through different mechanisms, such as involving the gut–brain and gut–muscle axis by various signaling pathways. This work advances the strategic integration of probiotics into the framework of predictive, preventive, and personalized medicine (PPPM) by demonstrating their dual capacity to directly enhance exercise performance and indirectly support immune, gastrointestinal, and cognitive function in athletes. Beyond compiling evidence, the findings illustrate a paradigm shift: probiotics are not merely adjuncts to health but potential precision tools that interact with the gut–muscle–brain axis to optimize physiological resilience and athletic adaptability. By contextualizing these effects within the personalized demands of modern sports and health care, this article affirms the necessity of incorporating probiotic-based interventions into individualized performance strategies and future PPPM applications, especially in diverse and resource-limited settings.

Meanwhile, probiotics have been considered as great means for modulating gut microbiota in a more favorable way. As several novel evidence has offered, probiotics can be helpful in enhancing humans’ health as well as preventing the diseases or reducing their severity. Regarding the effects of probiotics on athletes, it is revealed that probiotics are efficient in reducing the incidence and severity of infections, especially upper respiratory tract infections, in those individuals who are at more risk of infection due to suppressed immune system (Figs. 1 and 2). Furthermore, probiotics modulate the gastrointestinal symptoms of athletes which is induced by exercise, leading to higher rates of success and reducing the preventive effects of these symptoms on optimal performance. In addition to indirect effects of probiotics on athletes’ performance, studies have demonstrated that probiotics directly increase various performance-related factors, such as grip strength, competition time, psychological adaptation, and combating against exercise-induced fatigue. PPPM aims to transform healthcare by focusing on the early prediction of diseases, preventing their onset, and tailoring medical treatments to individual patients. In the context of gut microbiota and exercise, PPPM emphasizes the role of probiotics as a novel strategy to enhance health outcomes by modifying the composition and functions of the gut microbiota. The interplay between physical activity and gut microbiota is a burgeoning area of research, with growing evidence supporting the notion that exercise can beneficially alter microbiota composition, leading to improvements in metabolic health, immune function, and even mental well-being. Probiotics, which are live microorganisms that confer health benefits to the host, can further synergize with exercise regimens to optimize the gut environment. This tailored approach allows for the implementation of personalized probiotic interventions that are adjusted to an individual's unique microbiota profile and lifestyle, potentially enhancing exercise performance and recovery. Moreover, the preventive aspect underscores the importance of maintaining a balanced gut microbiome as a critical determinant of overall health and a deterrent against various diseases. Ultimately, this intersection of probiotics, exercise, and gut microbiota aligns seamlessly with the goals of PPPM by offering a pathway for personalized health strategies that can predict individual risk factors, prevent metabolic and inflammatory conditions, and personalize interventions for improved health outcomes. According to the PPPM, probiotics helps athletes control their oxidative stress, inflammatory indicators, and cognitive function while enhancing their athletic performance. This enables sports coaches to create more individualized plans. More athletes will be able to benefit from the PPPM since it is more effective and applicable in a variety of developing locations. As a key component for athletes in a wider variety of geographical areas, we advise that probiotic intake be included in future PPPM development and practical implementation.

Fig. 1.

Communication between gut and brain is a bilateral pathway which involves autonomic nervous system, the neuroendocrine system, the hypothalamic–pituitary–adrenal axis, the immune system, and metabolic pathways. GABA, γ-aminobutyric acid; 5-HT; 5-hydroxytryptamine

Fig. 2.

Presentation of probiotics'effects on athletes and their exercise performance through affecting metabolic pathways (such as increasing glycogen storage in muscles and liver), inflammatory signal pathways, and oxidative stress pathways. LA, lactic acid; IL, interleukin; iNOS, inducible nitric oxide synthase; MDA, malondialdehyde; GOT, glutamic-oxaloacetic transaminase; SOD, superoxide dismutase

Author Contribution

YL, YH, BM, ZW, BW involved in manuscript drafting and data collection.

Funding

This research was funded by the Guided Scientific Research Project of Shiyan Science and Technology Bureau (24Y055).

Data Availability

No datasets were generated or analysed during the current study.

Declarations

Competing interest

The authors declare no competing interests.