Gut microbiota is located in the intestinal lumen and can be affected by intestinal mucosal epithelial cells. Studies have found that the destruction of autophagy in intestinal epithelial cells can significantly change the composition of gut microbiota and reduce the alpha diversity of gut microbiota in mice (Soderholm and Pedicord, 2019). Exercise reduces the blood flow of intestinal organs and causes temporary hypoxia of intestinal epithelial cells with almost no difference in load intensity (Wu et al., 2020). Hypoxia activates autophagy (Li et al., 2022). In addition, specific knockout of Toll-like receptor4 (TLR4) intestinal epithelial cells can significantly affect the composition and function of gut microbiota related to lipid, amino acid and nucleotide metabolism (Soderholm and Pedicord, 2019). Aerobic exercise significantly reduces intestinal TLR4 in diabetic rats (Li et al., 2022), so it is speculated that exercise causes changes in gut microbiota through the above pathways.

Studies have also shown that temperature changes can cause changes in the diversity and composition of gut microbiota (Huus and Ley, 2021; Liu et al., 2023). For example, it has been shown that the β-diversity and composition of gut microbiota in free-wheeling mice changed significantly after exercise compared with non-exercise group. But this change did not occur at lower temperatures. Therefore, the authors suggest that exercise affects the composition of the gut microbiota by affecting core body temperature, including intestinal temperature (Sasaki et al., 2022). Some scholars believe that the influence of body temperature on gut microbiota may also be related to changes in metabolism, appetite and immune system function caused by temperature change (Huus and Ley, 2021), but the specific mechanism needs to be further studied. In addition, direct mechanical stimulation caused by exercise may be responsible for influencing the gut microbiota. For example, some studies suggest that exercise can enhance abdominal mechanical strength or promote the rapid passage of food through the colon by promoting the release of gastrointestinal hormones, thereby changing the PH value of the intestine and ultimately affecting the gut microbiota (Zhao et al., 2021).

The immune system may be an important mediator of the effects of exercise on gut microbiota. Both innate and adaptive immunity in the gut can affect the diversity and composition of gut microbiota (Yoo et al., 2020). Studies have shown that 2 weeks of moderate-intensity exercise and intermittent sprint exercise can effectively reduce circulating inflammatory factors and intestinal inflammatory markers, and increase the abundance of Bacteroidetes in people with insulin resistance. Reduce the ratio of Firmicutes/Bacteroidetes (Motiani et al., 2020). At the same time, due to the possible symbiotic relationship between immune cells and gut microbiota, the number and function of immune cells also affect the expression of gut microbiota. For example, studies have found that if Natural Killer T (NKT) cells are lacking, the pro-inflammatory microbiota will be increased (Selvanantham et al., 2016), but mice that are only reduced in invariant NKT (iNKT) will have increased anti-inflammatory microbiota and improved intestinal inflammation (Shen et al., 2018). In addition, some studies have shown that this condition can also affect the number of circulating immune cells [such as increased CD16⁺CD56⁺ NK cells and decreased CD3⁺ cytotoxic T cells (Tai et al., 2018)] and the proliferation ability of T cells (Navarro et al., 2013). It was also found that the number of lymphocytes, memory helper T (Th) cells, naive, memory, and activated cytotoxic T (Tc) cells, natural killer (NK) cells, NKT cells, and B1 cells were significantly reduced in peripheral blood samples of marathon runners compared to healthy sedentary controls (Panagoulias et al., 2023). These studies suggest that exercise may affect the function of gut or circulating immune cells, which in turn may affect the gut microbiota.

There is a brain-gut regulatory axis in the body, which is a bidirectional regulatory pathway, which is crucial for maintaining the homeostasis of the central nervous system and gastrointestinal tract. The brain can affect gut microbiota through the nervous system (sympathetic, parasympathetic) and endocrine (such as HPA axis, the hypothalamic–pituitary–adrenal axis) pathways (Hanscom et al., 2021). For example, studies have found that the use of drugs that reduce sympathetic nervous system excitability can attenuate the effects of exercise on gut microbiota (Sasaki et al., 2022). In addition, studies have shown that some patients with mental disorders have abnormal HPA axis function (most of them are hyperactive), and the composition of gut microbiota is different from that of healthy people. Therefore, some scholars believe that the nervous system can affect the gut microbiota through this endocrine pathway. At present, there are few direct studies on the relationship between exercise, HPA axis and gut microbiota. However, previous studies have shown that the activity of HPA axis is enhanced during exercise, but the negative feedback regulation of glucocorticoids will weaken the activity of HPA axis after exercise (Caplin et al., 2021). This may improve the disorder of gut microbiota caused by spirit, stress and other factors (Xie et al., 2022). But the results need further validation.

In addition to affecting gut microbiota through other systems, muscle contraction during exercise may also directly or indirectly cause changes in gut microbiota, and some muscle factors may play a role in this process. Irisin is a muscle factor secreted by exercise (Bilski et al., 2020), and it has also been found that exogenous irisin can effectively reverse the changes of gut microbiota caused by enteritis in mice (Huangfu et al., 2021). Therefore, irisin may mediate the changes in gut microbiota caused by exercise in diseases such as enteritis. TITIN, also known as C1q tumor necrosis factor-related protein 15 (CTRP15), is a newly discovered muscle factor that is released from rodent and human skeletal muscle in an exercise-induced manner (Tan et al., 2022; Shira et al., 2024). TITIN contributes to glucose and lipid metabolism; in addition, TITIN is positively correlated with IL-6 and TNF-α, suggesting its possible involvement in the inflammatory process (Shokoohi Nahrkhalaji et al., 2022). Among them, excessive glucose and fat intake can lead to the imbalance of gut microbiota (Zhang, 2022; Zeng et al., 2024). IL-6 deficiency can cause gut microbiota imbalance in mice (Wu et al., 2022). In a study of adolescents with depression, the content of Bifidobacterium in the gut microbiota of subjects was negatively correlated with the level of TNF-α (Chen X. et al., 2024). Therefore, it is speculated that TITIN may affect gut microbiota through some way. However, although some studies have found that some training modes (such as high-intensity interval training) can cause an increase in TITIN levels, not all training modes can cause changes in TITIN levels, which are related to the physiological conditions of the subjects themselves (Petro et al., 2024; Özçatal et al., 2023).

At present, there is little direct evidence that muscle factors affect gut microbiota, and the mechanism of action of muscle factors on gut microbiota needs to be further studied.

In conclusion, there are two types of mechanisms (multiple pathways) of direct and indirect effects of exercise on gut microbiota, but the two are not independent (as shown in Figure 1). However, the specific action process of each mechanism has not been fully elucidated. Whether different exercise loads have different effects on different mechanisms needs to be further studied.

At present, there are relatively few studies on the mechanism of the direct effect of gut microbiota on exercise, and most of them are on the effect of gut microbiota on muscle. Studies have found that the effect of gut microbiota on muscle may be achieved by affecting protein and amino acid metabolism. For example, Lahiri et al. found that germ-free mice had lower skeletal muscle weight, fewer muscle fibers, higher expression of genes regulating skeletal muscle-related protein degradation, and lower expression of genes regulating skeletal muscle differentiation by comparing various indicators of germ-free and pathogen-free mice (Lahiri et al., 2019). Qiu et al. (2021) found that after administering antibiotics orally for 4 weeks, the gut microbiota of C57BL/6 mice was inhibited, and skeletal muscle atrophy was observed, accompanied by disturbances in bile acid metabolism in the small intestine, decreased farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) in the ileum, decreased circulating FGF15, and decreased levels of ERK and its phosphorylation in skeletal muscle; In addition, it was found that supplementation with FGF19 partially reversed skeletal muscle atrophy. Therefore, the authors suggest that gut microbiota may partly regulate ERK protein in skeletal muscle through the FXR-FGF15/19 signaling pathway in the ileum, thereby affecting protein synthesis in skeletal muscle. In addition, we found that circulating and hepatic FGF21 gene expression in normal was increased after restricted protein diet. However, when germ-free mice were fed a restricted protein diet, circulating and hepatic FGF21 gene expression did not change. Therefore, it can be seen that microorganisms use FGF21 to cope with changes in protein content in food to promote the synthesis of essential amino acids for the host to use, thereby inhibiting sarcopenia. Therefore, it can be seen that microorganisms use FGF21 to cope with changes in protein content in food to promote the synthesis of essential amino acids for the host to use, thereby inhibiting sarcopenia (Martin et al., 2021). Other studies have suggested that gut microbiota can not only improve muscle endurance and strength by affecting glycogen storage and utilization by skeletal muscle, but also enhance mitochondrial respiration by affecting IGF-1 content, thereby improving skeletal muscle mass (Zhao et al., 2021). The gut microbiota can also influence muscle status through its metabolites. As one of the main metabolites of gut microbiota, short-chain fatty acids can be absorbed by the intestinal lumen and regulate the metabolism and function of skeletal muscle (Frampton et al., 2020). After feeding sterile mice aged 6–8 weeks with water containing short chain fatty acids, a metabolic product of gut microbiota, for 4 weeks, the skeletal muscle dimension significantly increased and muscle strength was improved. This may be due to a decrease in the expression of the Atrogin-1 gene that causes muscle atrophy, while an increase in the expression of the MyoD gene that reflects muscle formation (Lahiri et al., 2019). Similar results have been obtained in human experiments. In the body of sarcopenia patients, the content of gut microbiota (such as Faecalibacterium prausnitzii) with the ability to metabolze SCFA is significantly reduced (Prokopidis et al., 2021). In menopausal women, metagenomic association analysis has found that the ability of intestinal microorganisms to synthesize SCFA butyrate is increased, which is significantly correlated with serum butyrate level and skeletal muscle index, and there is a causal relationship between intestinal butyrate synthesis and limb lean mass (Lv et al., 2021). A survey of 412 children found that the more SCFA in their feces, the greater their lean body mass and muscle mass in their limbs (Chen et al., 2022).

The reason why SCFA promote skeletal muscle synthesis and metabolism may be related to reducing the absorption of intestinal inflammatory substances and improving the inflammatory state of the body; In addition, it may also be related to the G protein receptor pathway promoting the secretion of glucagon like peptide-1 and casein, increasing insulin sensitivity, promoting mitochondrial synthesis, increasing type I muscle fiber composition, and promoting myoglobin expression (Prokopidis et al., 2021). In addition, some scholars have found that the relationship between SCFA and muscle mass in children is influenced by the body fat content of the subjects (Chen et al., 2022), suggesting that there may be an indirect pathway between gut microbiota metabolites and skeletal muscle mass. Based on the above research, it can be seen that the impact of gut microbiota on skeletal muscle quality is closely related to short chain fatty acids. However, further research is needed to investigate the effects and mechanisms of SCFA on gut microbiota, as well as whether there are age differences.

Studies suggest that there is a gut-brain regulatory axis in the body, and gut microbiota plays an important role in this regulatory axis. Some scholars have proposed the “microbiota-gut-brain” axis. Studies have shown that gut microbiota can affect the development and function of the nervous system from multiple ways (Cryan et al., 2019). Current studies have found that the influence of gut microbiota on motor behavior may be achieved by affecting the function of the nervous system. For example, some studies have shown that flies in the sterile state show hyperactive behavior, which is characterized by accelerated movement speed and increased daily activity, while the transplantation of specific microbiota has the opposite change, and this effect is involved in the neurons in the upper and lower esophageal regions of Drosophila (Schretter et al., 2018).

Gut microbiota through the nervous system may not only affect exercise behavior but also affect cardiopulmonary function. For example, in the study by Vicentini et al. (2021) it was found that after antibiotic treatment of adult mice, the neurons or glial cells in the small intestine were lost or reduced. After restoring the gut microbiota, the number of neurons and glial cells increased. In addition, studies have shown that gut microbiota can regulate microglia homeostasis and promote their death. Metabolites of gut microbiota, such as isoamyl amine (IAA), can induce apoptosis of microglia by activating the S100 calcium binding protein A8 (S100A8) signaling pathway (Loh et al., 2024). At the same time, some studies have shown that glutamate released by microglia is an important excitatory neurotransmitter that controls the heart and lung centers. In the study by Zoccal et al, glutamate injection was able to increase sympathetic nerve activity in the abdomen and chest of mice exposed to chronic intermittent hypoxia for 10 days and enhance cardiopulmonary function (Cohen et al., 2018). Therefore, gut microbiota can affect exercise capacity by changing the number and function of nerve cells.

In addition to this indirect approach, gut microbiota can also affect the levels of certain neurotransmitters, such as serotonin (5-HT) and gamma aminobutyric acid (GABA), which in turn affect the function of the nervous system (Cryan et al., 2019). Research has shown that drugs that increase the concentration of extracellular 5-HT often reduce the excitability of the human motor cortex and enhance the excitability of spinal motor neurons (Thorstensen et al., 2024). The regulation of GABA levels can enhance the recruitment of the sensory motor cortex. In addition, lower GABA levels are associated with poorer motor performance in older adults (Maes et al., 2022). However, the effect of gut microbiota on exercise capacity through this pathway needs to be further demonstrated.

At present, the mechanism by which gut microbiota affects exercise capacity through the nervous system is not fully understood. However, given the controlling and coordinating role of the nervous system in body function, the influence of gut microbiota on motor ability through the nervous system will be a promising research field.

In addition to muscle and nervous system pathways, gut microbiota also has an impact on exercise capacity through immune and metabolic pathways. Research has found that Lactobacillus rhamnosus can regulate the proliferation of intestinal T lymphocytes, thereby modulating host immune function (Shonyela et al., 2020). Supplementing probiotics can regulate serum cytokines and secreted immunoglobulin A, as well as the quantity and activity of innate and adaptive immune cells, and reduce post exercise inflammatory responses (Donati Zeppa et al., 2019). In addition, gut microbiota can influence exercise capacity through metabolic pathways. For example, research has found that supplementing with appropriate probiotics can improve the efficiency of energy supply in the body, play a role in promoting glucose uptake in skeletal muscle cells, increase gut microbiota-produced SCFA (such as acetate), and promote ATP production in skeletal muscle cells (Chen et al., 2022), delaying the occurrence of exercise-induced fatigue (Donati Zeppa et al., 2019). In the study by Cheng et al., it was found that Lactiplantibacillus plantum TWK10 could reduce lactate production by promoting oxidation of fatty acids, and the administration of heat-inactivated TWK10 for 6 weeks showed potential benefits in anti-fatigue by reducing lactate and ammonia production during exercise (Cheng et al., 2023). The metabolic kinetic pathway of lactate labeled with isotope 13C3 showed that lactate accumulated in the blood after exercise could be transported to the intestine and metabolized to propionic acid by Veillonella, delaying fatigue and improving exercise capacity (Scheiman et al., 2019).

There are few targeted studies on the effect of gut microbiota on exercise capacity, and the research results are mostly concentrated in the fields of disease and nutrition. The research content mainly focuses on muscle metabolism, inflammatory response, and nerve action (Figure 2). Therefore, the direct relationship and mechanism between gut microbiota and sports ability (especially competitive sports ability and sports quality) are not clear.