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Cited by 583Gut microbiota and healthProbiotics and Fermented FoodsGastrointestinal motility and disorders

Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes

Open access
Clark, Allison, Mach, Núria·2016·Journal of the International Society of Sports Nutrition
DOI 10.1186/s12970-016-0155-6PMC PMC5121944
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Abstract

Fatigue, mood disturbances, under performance and gastrointestinal distress are common among athletes during training and competition. The psychosocial and physical demands during intense exercise can initiate a stress response activating the sympathetic-adrenomedullary and hypothalamus-pituitary-adrenal (HPA) axes, resulting in the release of stress and catabolic hormones, inflammatory cytokines and microbial molecules. The gut is home to trillions of microorganisms that have fundamental roles in many aspects of human biology, including metabolism, endocrine, neuronal and immune function. The gut microbiome and its influence on host behavior, intestinal barrier and immune function are believed to be a critical aspect of the brain-gut axis. Recent evidence in murine models shows that there is a high correlation between physical and emotional stress during exercise and changes in gastrointestinal microbiota composition. For instance, induced exercise-stress decreased cecal levels of Turicibacter spp and increased Ruminococcus gnavus, which have well defined roles in intestinal mucus degradation and immune function.Diet is known to dramatically modulate the composition of the gut microbiota. Due to the considerable complexity of stress responses in elite athletes (from leaky gut to increased catabolism and depression), defining standard diet regimes is difficult. However, some preliminary experimental data obtained from studies using probiotics and prebiotics studies show some interesting results, indicating that the microbiota acts like an endocrine organ (e.g. secreting serotonin, dopamine or other neurotransmitters) and may control the HPA axis in athletes. What is troubling is that dietary recommendations for elite athletes are primarily based on a low consumption of plant polysaccharides, which is associated with reduced microbiota diversity and functionality (e.g. less synthesis of byproducts such as short chain fatty acids and neurotransmitters). As more elite athletes suffer from psychological and gastrointestinal conditions that can be linked to the gut, targeting the microbiota therapeutically may need to be incorporated in athletes’ diets that take into consideration dietary fiber as well as microbial taxa not currently present in athlete’s gut.

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review argues that intense exercise-induced stress activates the SAM/HPA axes and the gut-microbiota-brain axis, contributing to gastrointestinal distress, mood disturbance, fatigue, and underperformance in athletes. It suggests that athlete diets low in fiber may reduce microbiota diversity and SCFA/neurotransmitter production, while prebiotics/probiotics and complex plant polysaccharides are promising but preliminary interventions.

Key findings

  • Exercise-induced stress affects an estimated 20–60% of athletes, and gastrointestinal symptoms affect 20–50%; in 29 highly trained male triathletes, 93% reported digestive disturbances during competition. Among exhausted marathon runners, 81% showed endotoxemia, 2% had lethal levels above 1 ng/mL, and 58 of 72 with high LPS levels reported GI upset versus 3 of 17 with low plasma endotoxin.
  • Stress hormone release has an intensity threshold around 50–60% VO2max; exercising at 80% capacity significantly increased ACTH, and 60–80% of athletes in early chronic stress showed higher pituitary CRH-stimulated ACTH responses.
  • In murine exercise models, forced treadmill running increased Ruminococcus gnavus versus sedentary controls, along with Butyrivibrio spp., Oscillospira spp., and Coprococcus spp., while Turicibacter spp. were lower in voluntary runners than in forced runners. Voluntary wheel running increased cecal N-butyrate to 8.14 ± 1.36 mmol/g versus 4.87 ± 0.41 mmol/g in controls.
  • Diet can account for up to 57% of gut microbiota changes versus no more than 12% for genes, and short-term animal- or plant-based diets can alter microbiota as fast as 24 hours. ADA athlete guidelines recommend high simple carbohydrate intake (6–10 g/kg/day), protein 1.2–1.7 g/kg/day, and low fat and fiber, but low fiber is associated with reduced microbiota diversity and SCFA production.

Methods

  • Design: the paper describes itself as a systematic review and provides a narrative synthesis of evidence on exercise-induced stress, the gut-microbiota-brain axis, and diet in athletes, with a secondary aim of defining dietary strategies.
  • Data: published human athlete studies and murine/animal models covering stress hormones, intestinal permeability and endotoxemia, microbiota composition, SCFAs, and probiotics/prebiotics; two summary tables are included.
  • Analysis: narrative synthesis; no meta-analysis is reported. The paper does not report search databases, inclusion/exclusion criteria, or risk-of-bias assessment.

Limitations

  • The paper states that there is no consensus on which symptoms or biomarkers define stress, that defining standard diet regimes is difficult because of the complexity of elite athlete stress responses, and that the role of microbiota in controlling exercise-induced stress adaptation remains unknown.
  • The paper states that only one study has shown exercise-induced stress directly modifies gut microbiota composition in non-germ-free or specific-pathogen-free animals, and that solid evidence demonstrating gut microbiota causality in stress is still missing.
  • Evident from the text: the evidence base is largely preliminary, animal-based, or from small human studies, and the review lacks a formal systematic search strategy, quality appraisal, or meta-analysis.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1186/s12970-016-0155-6

Cites

169 of 169 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 267 cited sources checked · 0 supported · 0 flagged

  • Premisenone given

    Recent evidence in murine models shows a high correlation between physical and emotional stress during exercise and changes in gastrointestinal microbiota composition.

    “Recent evidence in murine models shows that there is a high correlation between physical and emotional stress during exercise and changes in gastrointestinal microbiota composition.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Intense exercise activates the sympatho-adrenomedullary (SAM) and hypothalamus-pituitary-adrenal (HPA) axes.

    “Two main distinct but interrelated systems that affect the stress response during exercise are: the sympatho-adrenomedullary (SAM) and hypothalamus-pituitary-adrenal (HPA) axes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Ulrich-Lai YM, 2009, Nat Rev Neurosci source

      Not checked in the free run.

  • Premisecitation

    Diet dramatically modulates the composition of the gut microbiota.

    “Diet is known to dramatically modulate the composition of the gut microbiota.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] Fasano A, 2012, Clin Rev Allergy Immunol source

      Not checked in the free run.

  • Premisecitation

    Stress during exercise activates the autonomic nervous system (ANS).

    “Stress during exercise also activates the autonomic nervous system (ANS) [7]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Martins AS, 2005, Hypertension source

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  • Interpretationcitation

    NPY may play a role in reducing the stress response upon intense exercise.

    “Though few studies have studied serum and hippocampal NPY levels in response to exercise, these results suggest it plays a role in reducing the stress response upon intense exercise [41].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [41] Ramson R, 2012, Eur J Appl Physiol source

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  • May combine two claims. 104
  • Classified as probably not a substantial claim. 32

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    Premisecitation

    Induced exercise-stress decreased cecal levels of Turicibacter spp and increased Ruminococcus gnavus.

    “For instance, induced exercise-stress decreased cecal levels of Turicibacter spp and increased Ruminococcus gnavus, which have well defined roles in intestinal mucus degradation and immune function.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Allen JM, 2015, J Appl Physiol (1985) source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Other ways of communication between the gut-brain axis are gut hormones and gut microbiota molecules.

    “Other ways of communications between the gut-brain axis are: (i) gut hormones [9] (i.e. gamma aminobutyric acid (GABA), neuropeptide Y, dopamine) and (ii) gut microbiota molecules [10, 11] (i.e. short chain fatty acids (SCFA), tryptophan).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [9] Rhee SH, 2009, Nat Rev Gastroenterol Hepatol source

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    • cites [10] Lyte M, 2011, Cell Tissue Res source

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    • cites [11] Stilling RM, 2014, Genes Brain Behav source

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  • May combine two claims.

    Premisenone given

    The gut microbiome influences host behavior, intestinal barrier and immune function and is a critical aspect of the brain-gut axis.

    “The gut microbiome and its influence on host behavior, intestinal barrier and immune function are believed to be a critical aspect of the brain-gut axis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Exercise-induced stress results in activation of preganglionic sympathetic neurons in the thoracolumbar spinal cord, increasing circulating catecholamines.

    “Briefly, exercise-induced stress results in activation of preganglionic sympathetic neurons in the intermediolateral cell column of the thoracolumbar spinal cord (shown in purple and clear grey). This sympathetic activation represents the classic 'fight or flight' response and it generally increases circulating levels of catecholamines.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Ulrich-Lai YM, 2009, Nat Rev Neurosci source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Activation of the SAM and HPA axes results in the release of catecholamines and glucocorticoids into the circulatory system.

    “The activation of these axes results in the release of catecholamines (norepinephrine (NE) and epinephrine) and glucocorticoids into circulatory system (reviewed by Ulrich-Lai et al [6]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Ulrich-Lai YM, 2009, Nat Rev Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dietary recommendations for elite athletes are primarily based on a low consumption of plant polysaccharides, which is associated with reduced microbiota diversity and functionality.

    “What is troubling is that dietary recommendations for elite athletes are primarily based on a low consumption of plant polysaccharides, which is associated with reduced microbiota diversity and functionality (e.g. less synthesis of byproducts such as short chain fatty acids and neurotransmitters).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Rodriguez NR, 2009, Med Sci Sports Exerc source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Preliminary experimental data from probiotics and prebiotics studies indicate that the microbiota acts like an endocrine organ and may control the HPA axis in athletes.

    “some preliminary experimental data obtained from studies using probiotics and prebiotics studies show some interesting results, indicating that the microbiota acts like an endocrine organ (e.g. secreting serotonin, dopamine or other neurotransmitters) and may control the HPA axis in athletes.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Findings from murine models on exercise-induced stress and gut microbiota can be generalised to human athletes.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The bidirectional communication between the ANS and the enteric nervous system in the GI tract, the gut-brain axis, mainly occurs by way of the vagus nerve.

    “The bidirectional communication between the ANS and the enteric nervous system (ENS) in the GI tract, the gut-brain axis, mainly occurs by way of the vagus nerve, which runs from the brain stem through the digestive tract and regulates almost every aspect of the passage of digested material through the intestines (reviewed by Eisenstein [8]).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] Eisenstein M, 2016, Nature source

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    Premisecitation

    Proper intestinal barrier function is crucial for maintaining immune and overall health.

    “Proper intestinal barrier function is crucial for maintaining immune and overall health [53].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [53] de Oliveira EP, 2014, Sports Med source

      Not checked in the free run.

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    Premisecitation

    The aberrant stress response in germ-free mice was partially reversed by colonization with fecal matter from SPF animals and fully reversed by mono association of Bacillus infantis in a time dependent manner.

    “This aberrant stress response in GF mice was partially reversed by colonization with fecal matter from SPF animals and fully reversed by mono association of Bacillus infantis in a time dependent manner [47].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47] Sudo N, 2004, J Physiol source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Within the HPA axis, stress activates hypophysiotropic neurons in the PVN that secrete CRH and AVP, which act on the anterior pituitary to promote ACTH secretion, which acts on the adrenal cortex to release glucocorticoids.

    “Within the HPA axis, stress activates hypophysiotropic neurons in the paraventricular nucleus of the hypothalamus (PVN) that secrete releasing hormones, such as corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP), into the portal circulation of the median eminence. These releasing hormones act on the anterior pituitary to promote the secretion of adrenocorticotropic hormone (ACTH”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Ulrich-Lai YM, 2009, Nat Rev Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ruminococcus gnavus was increased in the forced group compared to sedentary group, together with Butyrivibrio spp., Oscillospira spp., and Coprococcus spp.

    “Additionally, Ruminococcus gnavus, which has well defined roles in intestinal mucus degradation, was increased in the forced group compared to sedentary group [52], together with Butyrivibrio spp., Oscillospira spp., and Coprococcus spp.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Allen JM, 2015, J Appl Physiol (1985) source

      Not checked in the free run.

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    Premisecitation

    Excessive release of stress hormones induced by physical and psychological stress can cause LPS translocation outside of the GI tract, triggering immune and inflammatory responses often resulting in increased intestinal permeability.

    “An excessive release of stress hormones induced by physical and psychological stress can cause lipopolysaccharides (LPS) translocation outside of the GI tract triggering immune and inflammatory responses often resulting in increased intestinal permeability [56].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [56] Brown WM, 2015, Sports Med Open source

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    Premisecitation

    Moderate exercise can increase GABA levels in the hypothalamus, resulting in lower resting blood pressure, heart rate and sympathetic tone.

    “Moderate exercise can increase GABA levels in the hypothalamus resulting in lower resting blood pressure, heart rate and sympathetic tone [39].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Hsu YC, 2011, J Hypertens source

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    Interpretationcitation

    Physical activity can alter microbiota composition as well as metabolic function that could either positively or negatively affect performance.

    “This preliminary study in exercised and stressed-animals shows that physical activity can alter microbiota composition as well as metabolic function that could either positively or negatively affect performance.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [52] Allen JM, 2015, J Appl Physiol (1985) source

      Not checked in the free run.

    • Rests on an assumption: Findings from murine models on exercise-induced stress and gut microbiota can be generalised to human athletes.

  • May combine two claims.

    Premisecitation

    Dopamine production is dependent upon levels of its precursor tyrosine, enteric bacteria that directly produce dopamine, the type of stress experienced and sex.

    “Dopamine production is dependent upon several factors: levels of its precursor tyrosine, enteric bacteria that directly produce dopamine, the type of stress experienced and sex [43].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Eisenhofer G, 1997, J Clin Endocrinol Metab source

      Not checked in the free run.

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    Premisecitation

    Forced swimming at 35°C caused an increase in hippocampal GABA to 120% of baseline, suggesting a stimulatory effect of psychological stress.

    “This later stressor, like novelty, caused an increase in hippocampal GABA (120% of baseline), suggesting a stimulatory effect of psychological stress [40].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] de Groote L, 2007, Neuroscience source

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  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Microorganisms that colonize the digestive tract can regulate the HPA axis through the regulation or production of short chain fatty acids and neurotransmitters such as GABA, dopamine and serotonin, as well as cytokines.

    “Microorganisms that colonize the digestive tract can be involved in the regulation of the HPA axis through the regulation or production of short chain fatty acids and neurotransmitters such as GABA, dopamine and serotonin, as well as cytokines.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    NPY is released in response to various stress stimuli, such as intense exercise, in the GI tract and plays a role in attenuating the HPA axis.

    “NPY is also released in response to various stress stimuli, such as intense exercise, in the GI tract and plays a role in attenuates the HPA axis [41].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Ramson R, 2012, Eur J Appl Physiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dietary changes can account for up to 57% of gut microbiota changes, whereas genes account for no more than 12%.

    “Dietary changes can account for up to 57% of gut microbiota changes, whereas genes account for no more than 12% [25].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Zhang C, 2010, ISME J source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A systematic review on endurance exercise and gut microbiota suggested that gut microbiota might have a key role in controlling oxidative stress and inflammatory responses as well as improving metabolism and energy expenditure during intense exercise.

    “A systematic review on endurance exercise and gut microbiota [23] suggested that gut microbiota might have a key role in controlling the oxidative stress and inflammatory responses as well as improving metabolism and energy expenditure during intense exercise.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Mach N and Fuster-Botella D: Endurance exercise and gut microbiota: A review. J Sport Health Sci 2016 (In press). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The human gut harbors more than 100 trillion microorganisms in the GI tract, representing roughly 9 million genes.

    “The human gut harbors more than 100 trillion microorganisms in the GI tract, which represents roughly 9 million genes [12].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Li J, 2014, Nat Biotechnol source

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    Premisecitation

    Voluntary wheel running for 6 weeks attenuated symptoms, whereas forced treadmill running exacerbates intestinal inflammation and clinical outcomes in a colitis mouse model.

    “Voluntary wheel running for 6 weeks attenuated symptoms, whereas forced treadmill running exacerbates intestinal inflammation and clinical outcomes in a colitis mouse model [52].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [52] Allen JM, 2015, J Appl Physiol (1985) source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The gut microbiota promotes digestion and food absorption for host energy production and provides folate, vitamin K2 and SCFAs.

    “The gut microbiota promotes digestion and food absorption for host energy production [14–16] and provide folate [17], vitamin K2 [18] and SCFAs [19].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [14] Hsu YJ, 2015, J Strength Cond Res source

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    • cites [15] Mach N, 2015, Environ Microbiol Rep source

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    • cites [16] Ramayo-Caldas Y, Mach N, Lepage P, et al.: Phylogenetic network analysis applied to pig gut microbiota identifies an ecosystem structure linked with growth traits. ISME 2016 (In press). source

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    • cites [17] Sugahara H, 2015, Biosci Microbiota Food Health source

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    • cites [18] Marley MG, 1986, Biochemistry source

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  • May combine two claims.

    Premisecitation

    Germ-free mice treated with Clostridium species, fecal flora from SPF mice or E. coli showed elevated levels of free catecholamines, suggesting that the gut microbiota plays a role in their synthesis through dopamine regulation.

    “Moreover, GF mice treated with Clostridium species, fecal flora from the SPF mice or E. coli showed elevated levels of free catecholamines suggesting that the gut microbiota plays a role in their synthesis through dopamine regulation [48].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48] Asano Y, 2012, Am J Physiol Gastrointest Liver Physiol source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Acetate, propionate, and N-butyrate are present at a molar ratio of approximately 60:20:20 in the colon and feces.

    “Acetate, propionate, and N-butyrate are present at a molar ratio of approximately 60:20:20 in the colon and feces [74].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [74] den Besten G, 2013, J Lipid Res source

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  • May combine two claims.

    Premisecitation

    In healthy young adult male cyclists performing endurance sports 4-10 hours per week, one hour of physical activity at 70% maximum workload capacity produced splanchnic hypoperfusion, which can cause decreased GI circulation, increased intestinal permeability and damage to the small intestine.

    “In healthy young adult male cyclists who performed endurance sports activities during 4–10 hours per week, just one hour of physical activity at 70% maximum workload capacity produced splanchnic hypoperfusion, which can cause decreased GI circulation, increased intestinal permeability and damage to the small intestine [64].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [64] van Wijck K, 2012, Am J Physiol Gastrointest Liver Physiol source

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  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    The microbiota's production of butyrate and propionate can increase transepithelial resistance, which improves intestinal barrier function and decreases inflammation.

    “Conversely, the microbiota’s production of butyrate and propionate can increase transepithelial resistance, which improves intestinal barrier function and decreases inflammation.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Glucocorticoids released during intense exercise diminish TLR expression, and therefore the capacity to produce anti-inflammatory cytokines and host antimicrobial defense.

    “Glucocorticoids released during intense exercise has also been shown to diminish the TLR expression, and therefore the capacity to produce anti-inflammatory cytokines and host antimicrobial defense [68].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Gleeson M, 2007, J Appl Physiol (1985) source

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    Premisecitation

    Translocated LPS are detected by CD14 and TLR4, which causes the release of pro-inflammatory cytokines such as TNFα, IFNα, INFγ and interleukins (IL1β or IL6), which can eventually result in endotoxemia.

    “The translocated LPS are detected by CD14 and toll-like receptor 4 (TLR4), which causes the release of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFα), interferon alpha (IFNα), interferon-gamma (INFγ) and interleukins (IL1β or IL6), which can eventually result in endotoxemia [57] (Fig. 2).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Zuhl M, 2014, Br J Sports Med source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The central fatigue hypothesis states that increased serotonin release is associated with sleep, drowsiness and central fatigue, which contribute to suboptimal physical performance.

    “The central fatigue hypothesis states that increased of the neurotransmitter serotonin (5-hydroxytryptamine; 5-HTP) release is associated with sleep, drowsiness and central fatigue, which contribute to suboptimal physical performance (reviewed by Best et al [82], Fig. 3).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [82] Best J, 2010, Theor Biol Med Model source

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  • May combine two claims.

    Premisecitation

    The cecum was approximately 1.5 times larger in the exercise group than in the control group, and cecal tissue weights and contents were much greater in the exercise group, indicating a significant change in the cecal environment in response to voluntary wheel running.

    “The cecum was approximately 1.5 times larger in the exercise group than in the control group, and the cecal tissue weights and contents were much greater in the exercise group than in the control group, indicating that a significant change had occurred in the cecal environment in response to voluntary wheel running [80].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [80] Matsumoto M, 2008, Biosci Biotechnol Biochem source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Hypoperfusion and ischemia can result in increased intestinal permeability, opening the door for LPS and enteric bacteria to circulate the bloodstream, possibly leading to endotoxemia.

    “Therefore hypoperfusion and ischemia can result in increased intestinal permeability opening the door for LPS and enteric bacteria to circulate the bloodstream, possibly leading to endotoxemia.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Exercise-induced stress can diminish intestinal barrier function and cause LPS translocation, resulting in GI upset, hydration imbalances, poor uptake of nutrients and electrolytes, thermal damage of the intestinal mucosa, all negatively affecting athletic performance.

    “In general, exercise-induced stress can diminish intestinal barrier function and cause LPS translocation which results in GI upset, hydration imbalances, poor uptake of nutrients and electrolytes, as well as thermal damage of the intestinal mucosa, all of which negatively affect athletic performance [64].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [64] van Wijck K, 2012, Am J Physiol Gastrointest Liver Physiol source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Intense exercise over a prolonged period increases stress hormones and LPS translocation in the gastrointestinal tract, which triggers immune responses that often result in increased pro-inflammatory cytokines and intestinal permeability.

    “Additionally, intense exercise over a prolonged period of time increase stress hormones and lipopolysaccharides (LPS) translocation in the gastrointestinal tract, which triggers immune responses that often results in increased pro-inflammatory cytokines and intestinal permeability.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Between 20-50% of athletes suffer gastrointestinal symptoms depending on exercise type, intensity, age and other factors, and these symptoms increase with exercise intensity.

    “Depending on the type of exercise, intensity, age and other factors, between 20-50% of athletes suffer gastrointestinal symptoms, which have been shown to increase with exercise intensity [60].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Lamprecht M, 2012, J Int Soc Sports Nutr source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In the colon and cecum, complex plant-derived polysaccharides are digested and fermented by gut microorganisms into SCFAs and gases, which are also used as carbon and energy sources by specialized bacteria.

    “In the colon and cecum, complex plant-derived polysaccharides are digested and subsequently fermented by gut microorganisms, such as Lactobacillus, Bifidobacterium, Clostridium, Bacteroides, into SCFAs and gases which are also used as carbon and energy sources by specialized bacteria such as reductive acetogens, sulfate-reducing bacteria and methanogens (reviewed by Marchesi et al [36] and by Flin”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [36] Marchesi JR, 2016, Gut source

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    • cites [19] Flint HJ, 2008, Nat Rev Microbiol source

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  • May combine two claims.

    Premisecitation

    The redistribution of blood flow away from the intestines together with thermal damage to the intestinal mucosa can cause intestinal barrier disruption, followed by an inflammatory response.

    “The redistribution of blood flow away from the intestines together with thermal damage to the intestinal mucosa can cause intestinal barrier disruption, followed by an inflammatory response [63].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [63] Lambert GP, 2009, J Anim Sci source

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  • May combine two claims.

    Interpretationcitation

    Intense exercise affects SCFA production, which in turn affects the HPA axis, GI health and may promote favorable athletic performance.

    “Although there are few studies that show the effect exercise has on SCFA levels in the cecum and energy metabolism, those that do exist, illustrate how intense exercise affect SCFA production, which in turn affects the HPA axis, the GI health and may promote favorable athletic performance.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Findings from rodent studies on exercise, gut microbiota, SCFA and neurotransmitters can be generalized to human athletes.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    About 2% of ingested tryptophan is used for the synthesis of serotonin.

    “According to a review conducted by Best et al [82], about 2% of ingested tryptophan is used for the synthesis of serotonin.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [82] Best J, 2010, Theor Biol Med Model source

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  • May combine two claims.

    Premisecitation

    During intense exercise, athletes' body temperature increases and blood pools away from the gastrointestinal tract to periphery muscles and organs such as the heart and lungs.

    “During intense exercise, athletes’ body temperature increases and blood pools away from the gastrointestinal tract to periphery muscles and organs such as the heart and lungs during intense physical activity [62].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [62] Qamar MI, 1987, Gut source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Redistribution of blood flow away from the intestines together with thermal damage to the intestinal mucosa can cause intestinal barrier disruption followed by an inflammatory response.

    “The redistribution of blood flow away from the intestines together with thermal damage to the intestinal mucosa can cause intestinal barrier disruption, followed by an inflammatory response [63].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [63] Lambert GP, 2009, J Anim Sci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Brock-Utne et al discovered that 81% of randomly selected exhausted marathon runners showed endotoxemia (0.1 ng/mL), 2% presented lethal levels above 1 ng/mL and only 19% had normal levels.

    “Brock-Utne et al [66] discovered that 81% of randomly selected exhausted marathon runners showed endotoxemia (0,1 ng/mL), 2% presented lethal levels above 1 ng/mL and only 19% had normal levels.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [66] Brock-Utne JG, 1988, S Afr Med J

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ischemia increases reactive oxygen species production, which induces leaky gut as activated protein kinases phosphorylate tight junction proteins resulting in hyperpermeability.

    “Ischemia also increases reactive oxygen species (ROS) production, which induces leaky gut as activated protein kinases phosphorylate tight junctions proteins resulting in hyperpermeability (Fig. 2) [57].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [57] Zuhl M, 2014, Br J Sports Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Hydrogen peroxide can activate transcription of pro-inflammatory genes including NFKβ, TNFα, IL6, IFNγ, and IL1β, which can compromise barrier function.

    “Hydrogen peroxide can also serve as a signaling molecule that activates transcription of several pro-inflammatory genes including nuclear factor kappa-light-chain-enhancer of activated B cells (NFKβ), TNFα, IL6, IFNγ, and IL1β [65] that can compromise barrier function.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [65] Holland AM, 2015, BMC Res Notes source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Low serotonin in the brain causes mood disorders and depression as well as changes in gut transit, blood pressure, cardiac function and platelet aggregation.

    “Furthermore, low serotonin in the brain also causes mood disorders and depression as well as changes in gut transit, blood pressure, cardiac function and platelet aggregation (reviewed by Evans et al [83], Fig. 3).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [83] Evans JM, 2013, J Endocrinol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Activation of the HPA axis may stimulate subepithelial mast cells to secrete immune mediators such as histamine, proteases and pro-inflammatory cytokines, triggering intestinal permeability.

    “Additionally, the activation of the HPA axis may stimulate subepithelial mast cells to secrete immune mediators such as histamine, proteases and pro-inflammatory cytokines [58], trigging intestinal permeability [59].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [58] Ferrier L, 2008, Gut source

      Not checked in the free run.

    • cites [59] Wallon C, 2008, Gut source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Intense exercise during prolonged periods can lead to increased intestinal permeability and thus increased plasma LPS levels, and can also cause immunosuppression.

    “All these studies show that intense exercise during prolonged periods not only can lead to increased intestinal permeability and thus increased plasma LPS levels, but it can also cause immunosuppression [69].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [69] Bosenberg AT, 1988, J Appl Physiol (1985) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a study of 29 highly trained male triathletes, 93% reported digestive disturbances upon competition and two participants abandoned the race because of severe vomiting and diarrhea.

    “In a study of 29 highly trained male triathletes, Jeukendrup et al [61] discovered that upon competition, 93% reported digestive disturbances and two participants had to abandon the race because of severe vomiting and diarrhea.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] Jeukendrup AE, 2000, Clin Sci (Lond) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Many athletes who suffer from stress enter a vicious cycle of overexerting themselves with strenuous training and competitions, which results in fatigue causing them to over train in order to overcome fatigue and decreased athletic performance.

    “Many athletes who suffer from stress enter into a vicious cycle of over exerting themselves with strenuous training and competitions, which results in fatigue causing them to over train in order to overcome fatigue and decreased athletic performance [4].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Purvis D, 2010, PM R source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Approximately 95% of the body's serotonin is produced in the enterochromaffin cells of the intestines, which plays a role in enteric motor and sensory functions such as visceral pain perception.

    “Approximately 95% of the body's serotonin is produced in the enterochromaffin cells (EC) of the intestines [8, 83], which plays a role in enteric motor and sensory functions such as visceral pain perception, further illustrating the gut-brain connection [84].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [8] Eisenstein M, 2016, Nature source

      Not checked in the free run.

    • cites [83] Evans JM, 2013, J Endocrinol source

      Not checked in the free run.

    • cites [84] Stasi C, 2012, J Gastroenterol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    N-butyrate and propionate can increase transepithelial resistance, which improves intestinal barrier function and decreases inflammation.

    “N-butyrate and propionate can increase transepithelial resistance which improves intestinal barrier function and decreases inflammation [78].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [78] Puddu A, 2014, Mediators Inflamm

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Marathon, triathlete and ultra endurance athletes have been reported to have plasma LPS concentrations of 5 to 284 pg/mL along with up to 93% of athletes reporting digestive disturbances, which could be caused by the LPS-induced cytokine response.

    “For instance, marathon, triathlete and ultra endurance athletes have been reported to have plasma LPS concentrations of 5 to 284 pg/mL along with up to 93% of athletes reporting digestive disturbances, which could be caused by the LPS-induced cytokine response [61].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] Jeukendrup AE, 2000, Clin Sci (Lond) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Premisecitation

    The central fatigue hypothesis is weak because there lacks evidence showing what specifically causes an increase in brain tryptophan during exercise.

    “Nevertheless, Fernstrom et al [95] state that the central fatigue hypothesis is weak because there lacks evidence that shows what specifically causes an increase in brain tryptophan during exercise [95].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [95] Fernstrom JD, 2006, J Nutr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dopamine cannot easily cross the blood-brain barrier; neurons must synthesize dopamine from its precursor tyrosine ingested from the diet.

    “Like 5-HTP, dopamine cannot easily cross the blood–brain barrier [97]; therefore, neurons must synthesize dopamine from its precursor tyrosine that’s ingested from the diet [97].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [97] Foley TE, 2008, Neuromolecular Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    5-HTP is rapidly decarboxylated by aromatic amino acid decarboxylase to produce cytosolic serotonin.

    “The 5-HTP is then rapidly decarboxylated by the aromatic amino acid decarboxylase (AADC) to produce cytosolic serotonin [82].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [82] Best J, 2010, Theor Biol Med Model source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    TPH1 is expressed in the periphery and pineal body, whereas TPH2 appears responsible for serotonin synthesis in the rest of the brain.

    “Of these enzymes, TPH1 is expressed in the periphery and in the pineal body, whereas TPH2 appears to be responsible for the synthesis of serotonin in the rest of the brain.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [87] McKinney J, 2005, J Neurochem source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Bifidobacterium infantis may have antidepressant effects and gut bacteria can modulate serotonin levels.

    “The authors concluded that this probiotic may have antidepressant effects and illustrates how gut bacteria can ultimately modulate serotonin levels [107].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [107] Desbonnet L, 2008, J Psychiatr Res source

      Not checked in the free run.

    • Rests on an assumption: Findings from rodent studies on exercise, gut microbiota, SCFA and neurotransmitters can be generalized to human athletes.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Dopamine is an important neurotransmitter associated with motivation and reward.

    “Moreover, dopamine is an important neurotransmitter associated with motivation and reward [97].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [97] Foley TE, 2008, Neuromolecular Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    IDO is stimulated by oxidative stress and pro-inflammatory cytokines such as IL6 and TFNα, which are released due to LPS-induced intestinal permeability during intense exercise.

    “IDO is stimulated by oxidative stress and pro-inflammatory cytokines such as IL6 and TFNα, which are released due to LPS-induced intestinal permeability experienced during intense exercise [89].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [89] Xie W, 2014, J Neuroinflammation source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Two distinct TPH genes exist in humans: TPH1 and TPH2.

    “However, Walther and et al [88] have reported the existence of two distinct TPH genes in humans: TPH1 and TPH2.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [88] Walther DJ, 2003, Science source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Glutamine is crucial for glutamate and GABA synthesis, optimal functioning of leukocytes such as lymphocytes and macrophages, T cell proliferation and function, and intestinal enterocytes growth.

    “Glutamine, a nonessential amino acid that’s the most abundant in the human body [102], is crucial not only for the glutamate and GABA synthesis but also for optimal functioning of leukocytes such as lymphocytes and macrophages, T cell proliferation and function [104], intestinal enterocytes growth [102].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [102] Desvergne B, 2006, Physiol Rev source

      Not checked in the free run.

    • cites [104] Mul JD, 2015, Prog Mol Biol Transl Sci source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Prolonged intense exercise could negatively affect neurotransmitter homeostasis and immune response when glutamine levels are depleted to detoxify ammonia in the brain, causing a more excitatory-glutamate driven response and a decline in GABA-mediated inhibitory pathways.

    “Therefore, prolonged intense exercise could negatively affect neurotransmitter homeostasis and immune response when glutamine levels are depleted [80, 81] in order to detoxify ammonia in the brain causing a more excitatory-glutamate driven response to exercise-induced stress and a decline in GABA-mediated inhibitory pathways.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [80] Matsumoto M, 2008, Biosci Biotechnol Biochem source

      Not checked in the free run.

    • cites [81] Gleeson M, 2007, J Appl Physiol source

      Not checked in the free run.

    • Rests on an assumption: Findings from rodent studies on exercise, gut microbiota, SCFA and neurotransmitters can be generalized to human athletes.

  • May combine two claims.

    Premisecitation

    In naive rats, Bifidobacterium infantis administered for 14 days had no effect on swim performance but significantly reduced IFNγ, TNFα and IL-6 and increased plasma tryptophan and kynurenic acid compared to controls.

    “Although the probiotic had no effect on swim performance, there was a significant reduction of IFNγ, TNFα and IL-6 in the probiotic-treated rats compared to controls, and there was a significant increase in plasma concentrations of tryptophan but also kynurenic acid in the bifidobacteria-supplemented rats.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [107] Desbonnet L, 2008, J Psychiatr Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Under stress, nutrient availability can affect energy metabolism and protein synthesis as well as endocrine, nervous and immune systems.

    “Under stress, nutrient availability has the potential to affect energy metabolism and protein synthesis as well as endocrine, nervous and immune systems [109].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [109] Desborough JP, 2000, Br J Anaesth source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Moderate aerobic exercise increases dopamine levels while reducing serotonin levels in the nigrostriatal tract.

    “On the other hand, moderate aerobic exercise has been shown to increase dopamine levels while reducing serotonin levels in the nigrostriatal tract [44], illustrating that exercise can greatly alter neurotransmitter metabolism.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Heijnen S, 2015, Front Psychol

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Glucocorticoids and pro-inflammatory cytokines induce TDO and IDO enzymes, leading to less serotonin synthesis and possibly fatigue and depression in athletes under stress.

    “Consequently, glucocorticoids and pro-inflammatory cytokines induce TDO and IDO enzymes leading to less serotonin synthesis and possibly fatigue and depression that many athletes who suffer from stress.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Increases in pro-inflammatory cytokines like IFNγ and IL6 are associated with reduced exercise tolerance, acute viral or bacterial infection and increased tryptophan catabolism, which could limit brain serotonin synthesis leading to depressive behavior.

    “Increases in pro-inflammatory cytokines like IFNγ and IL6 have been associated with reduced exercise tolerance, acute viral or bacterial infection and increased tryptophan catabolism which could thus limit brain serotonin synthesis [100], leading to depressive behavior.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [100] Dunn AJ, 2006, Clin Neurosci Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Germ-free rats had lower levels of tryptophan that increase after administering bifidobacteria species.

    “GF rats on the other hand had lower levels of tryptophan that increase after administering bifidobacteria species [107].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [107] Desbonnet L, 2008, J Psychiatr Res source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Altered dopaminergic pathways involving movement lead to fatigue.

    “It is suggested that altered dopaminergic pathways involving movement lead to fatigue (reviewed by Foley [97]).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [97] Foley TE, 2008, Neuromolecular Med source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    The gut microbiota serves as an endocrine organ facilitating production and regulation of various neurotransmitters and hormones, which can affect an athlete's mood, motivation, and sensation of fatigue.

    “As explained above, the gut microbiota serves as an endocrine organ in many ways facilitating the production and regulation of various neurotransmitters and hormones (Table 1), which can affect an athlete’s mood, motivation, and sensation of fatigue (Fig. 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The overall metabolic effect of hormonal changes is increased metabolism, mobilizing substrates for energy and retaining salt and water to maintain fluid volume, cardiovascular homeostasis and immune response.

    “The overall metabolic effect of the hormonal changes is increased metabolism, which mobilizes substrates to provide energy sources, and a mechanism to retain salt and water and maintain fluid volume, cardiovascular homeostasis and immune system response [109].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [109] Desborough JP, 2000, Br J Anaesth source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Once in the CNS, L-tryptophan is converted by tryptophan hydroxylase into 5-HTP, the rate limiting step in brain serotonin synthesis.

    “Once in the CNS, L-tryptophan is converted from tryptophan hydroxylase (TPH) into 5-HTP, the rate limiting step in brain serotonin synthesis [87].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [87] McKinney J, 2005, J Neurochem source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Exercise stimulates glutamine synthesis used for ammonia detoxification, resulting in decreased production of excitatory neurotransmitter glutamate possibly causing fatigue in endurance athletes.

    “These findings show that exercise stimulates glutamine synthesis that’s used for ammonia detoxification resulting in decreased production of the excitatory neurotransmitter glutamate possibly causing fatigue in endurance athletes [101].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [101] Guezennec CY, Abdelmalki A, Serrurier B, et al. Effects of prolonged exercise on brain ammonia and amino acids. Int J Sports Med. 1998;19:323–7. source

      Not checked in the free run.

    • Rests on an assumption: Findings from rodent studies on exercise, gut microbiota, SCFA and neurotransmitters can be generalized to human athletes.

  • May combine two claims.

    Premisecitation

    In trained and untrained rats that ran until exhausted, serum ammonia increased, which can reduce brain energy by stimulating the Krebs cycle and glycolysis.

    “They discovered that both trained and untrained rats that ran until exhausted presented an increase in serum ammonia, which can reduce brain energy by stimulating the Krebs cycle and glycolysis.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [101] Guezennec CY, Abdelmalki A, Serrurier B, et al. Effects of prolonged exercise on brain ammonia and amino acids. Int J Sports Med. 1998;19:323–7. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The trained exercise group had ammonia levels 50% higher than the untrained group and lower levels of glutamate and GABA in the striatum.

    “The trained exercise group had levels of ammonia 50% higher than the untrained group and also presented lower levels of the excitatory neurotransmitter glutamate as well as a decrease in GABA in the striatum of the brain [101].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [101] Guezennec CY, Abdelmalki A, Serrurier B, et al. Effects of prolonged exercise on brain ammonia and amino acids. Int J Sports Med. 1998;19:323–7. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Running at low speed appears to increase cerebral serotonin levels and decrease depressive and anxious behavior, whereas high-speed running causes an increase in gene expression of CRH.

    “When focusing to the interaction between serotonin and exercise, running at low speed appears to increase cerebral serotonin levels and decrease depressive and anxious behavior, whereas high-speed running causes an increase in the gene expression of CRH [93].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [93] Otsuka T, 2016, Beh Brain Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Low levels or absence of gut microbiota (germ-free animals) increase tryptophan and serotonin levels and modify central higher order behavior.

    “There is strong evidence that low levels or an absence of gut microbiota (i.e. GF animals) increase tryptophan and serotonin levels and modify central higher order behavior [106].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [106] Clarke G, 2013, Mol Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Adequate protein intakes enhance host immunity with particular effects on the T cell system, resulting in decreased incidences of infections.

    “Adequate protein intakes enhance host immunity with particularly effects on the T cell system, resulting in decreased incidences of infections.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Carabotti M, 2015, Ann Gastroenterol

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    High-fat diet microbiota can increase anxiety-like behaviour and neuro-inflammation and disrupt intestinal barrier function.

    “High-fat diet microbiota can increase anxiety-like behaviour and neuro-inflammation and disrupt intestinal barrier function [114].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [114] Achten J, 2004, J Appl Physiol (1985) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Protein intake of 1.2 to 1.6 g/kg per day is recommended in top elite athletes.

    “1.2 to 1.6 g/kg per day in the top elite athletes [41, 42]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [41] Ramson R, 2012, Eur J Appl Physiol source

      Not checked in the free run.

    • cites [42] Saunders PR, 2002, Dig Dis Sci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Low dietary fiber consumption is associated with lower microbiota diversity, fewer anti-pathogenic bacteria and less SCFA production.

    “Low dietary fiber consumption is associated with lower microbiota diversity, fewer anti-pathogenic bacteria and less SCFA production [146], which may lead to inflammation [122] and less sympathetic nervous system stimulation [123]”
    • Also stated in: § Dietary recommendations to reduce the exercise-induced stress behavior and symptoms and to improve the gut microbiota composition and function for athletes · plain
      “Low dietary fiber consumption is associated with lower microbiota diversity, less SCFA production [112] and fewer anti-pathogenic bacteria [153], all of which may have harmful long-term consequences for the host [112].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [146] Konig D, 1997, Exerc Immunol Rev

      Not checked in the free run.

    • cites [112] Sonnenburg ED, 2016, Nature source

      Not checked in the free run.

    • cites [153] Hold GL, 2014, Gut source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Low dietary fiber consumption may lead to inflammation and less sympathetic nervous system stimulation.

    “Low dietary fiber consumption is associated with lower microbiota diversity, fewer anti-pathogenic bacteria and less SCFA production [146], which may lead to inflammation [122] and less sympathetic nervous system stimulation [123]”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [122] Bruunsgaard H, 2000, Immunol Cell Biol source

      Not checked in the free run.

    • cites [123] Pasiakos SM, 2011, Am J Clin Nutr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Leucine supplementation can greatly increase leucine and total BCAA concentrations and improve endurance performance.

    “Leucine supplementation can greatly increase leucine and total BCAA concentrations and improve endurance performance [49] and muscle protein synthesis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] Bravo JA, 2011, Proc Natl Acad Sci U S A source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Elite athletes' dietary plans are based on consumption of certain micronutrients such as iron, calcium, amino acids, essential fatty acids and antioxidants, but rarely consider gut microbiota health.

    “Elite athletes’ dietary plans are also based on the consumption of certain micronutrients such as iron, calcium, amino acids, essential fatty acids and antioxidants [111], but rarely is the health of the gut microbiota ever considered.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [111] Antonio J, Stout JR, Willoughby D, et al.: Essentials of sports nutrition and supplements. International society of sports nutrition, Human Press 2008

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Polyphenol supplementation with blueberry and green tea extracts did not mitigate the physiological stress of heavy exertion nor improve recovery speed in athletes.

    “Although no negative effects have been reported, athletes´ diets enriched with polyphenol extracts (blueberry and green tea), they do not mitigate the physiological stress of heavy exertion nor do they improve recovery speed [120].”
    • Also stated in: § Dietary recommendations to reduce the exercise-induced stress behavior and symptoms and to improve the gut microbiota composition and function for athletes · plain
      “Although no negative effects have been reported, athletes’ diets enriched with polyphenol extracts (blueberry and green tea) have not mitigated the physiological stress of heavy exertion nor did it improve recovery speed [151].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [120] Krzwkowski K, 2001, J Appl Physiol source

      Not checked in the free run.

    • cites [151] Nieman DC, 2013, PloS One source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    An acute dose of oral glutamine 2 h before intense exercise may ameliorate stress-induced intestinal permeability, lower plasma endotoxins and be anti-inflammatory.

    “An acute dose of oral glutamine 2 h before intense exercise may ameliorate stress-induced intestinal permeability, lower plasma endotoxins and be anti-inflammatory [65]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [65] Holland AM, 2015, BMC Res Notes source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Tyrosine ingestion does not influence time to exhaustion or several aspects of cognitive function while exercising in heat conditions.

    “Tyrosine ingestion does not influence time to exhaustion or several aspects of cognitive function while exercising in heat conditions [99].”
    • Also stated in: § Dietary recommendations to reduce the exercise-induced stress behavior and symptoms and to improve the gut microbiota composition and function for athletes · plain
      “However, tyrosine ingestion does not influence time to exhaustion or several aspects of cognitive function while exercising in heat conditions [128].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [99] Sutton EE, 2005, Int J Sport Nutr Exerc Metab source

      Not checked in the free run.

    • cites [128] Watson P, 2012, Int J Sport Nutr Exerc Metab source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    An initial bacterial community is established at birth, but develops as a person matures.

    “An initial bacterial community is established at birth, but develops as a person matures [8].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] Eisenstein M, 2016, Nature source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    Since diet strongly influences microbiota composition and function, modulation of the gut microbiota via nutritional treatments may improve the stress response in athletes and improve performance.

    “Since diet strongly influences microbiota composition and function, modulation of the gut microbiota via nutritional treatments may improve the stress response in athletes and improve performance.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    BCAA supplementation may be effective at reducing fatigue by increasing ammonia production.

    “BCAA supplementation may be effective at reducing fatigue by increasing ammonia production”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Carbohydrates at 7 to 12 g/kg per day for athletes who train more than 2 h/day restore muscle and liver glycogen stores, attenuate stress hormone levels and immunosuppression, and reduce fatigue and improve performance and mood.

    “7 to 12 g/kg per day for athletes who train for more than 2 h/day [145] | Restore muscle and liver glycogen stores during intense exercise; Attenuate stress hormone levels and immunosuppression; Reduce fatigue and improve performance and mood [35].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [145] Pedersen L, 2016, Cell Metab source

      Not checked in the free run.

    • cites [35] Carabotti M, 2015, Ann Gastroenterol

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Adequate fiber intake is 14 g total fiber per 1,000 kcal, or 25 g for adult women and 38 g for adult men.

    “Adequate fiber intake is 14 g total fiber per 1,000 kcal, or 25 g for adult women and 38 g for adult men, based on research demonstrating protection against various diseases [121].”
    • Also stated in: § Dietary recommendations to reduce the exercise-induced stress behavior and symptoms and to improve the gut microbiota composition and function for athletes · boosted
      “The Academy of Nutrition and Dietetics has recently established that adequate fiber intake is 14 g total fiber per 1,000 kcal, or 25 g for adult women and 38 g for adult men, based on research demonstrating protection against coronary heart disease among diseases [152].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [121] Kingsbury KJ, 1998, Br J Sports Med source

      Not checked in the free run.

    • cites [152] Dahl WJ, 2015, J Acad Nutr Diet source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Inadequate protein intake impairs host immunity with particularly detrimental effects on the T cell system, resulting in increased incidences of infections.

    “Inadequate protein intake impairs host immunity with particularly detrimental effects on the T cell system, resulting in increased incidences of infections [113].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [113] Gleeson M, 2000, Immunol Cell Biol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Leucine supplementation results in significant increases in plasma leucine and total branched chain amino acids concentrations and improves endurance performance and upper body power, affecting the plasma tryptophan: BCAA ratio.

    “Leucine supplementation resulted in significant increases in plasma leucine and total branched chain amino acids concentrations and improved endurance performance and upper body power, affecting the plasma tryptophan: BCAA ratio [124].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [124] Crowe MJ, 2006, Eur J Appl Physiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    High carbohydrate diets (8.5 g/Kg/d; 65% total energy intake) and eating carbohydrates ad libitum during intense periods of training can reduce fatigue and improve physical performance and mood.

    “High carbohydrate diets (8.5 g/Kg/d; 65% total energy intake) [114] and eating carbohydrates ad libitum during intense periods of training can reduce fatigue and improve physical performance and mood [115].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [114] Achten J, 2004, J Appl Physiol (1985) source

      Not checked in the free run.

    • cites [115] Morgan WP, 1988, Med Sci Sports Exerc source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The combination of glucose and fructose results in higher carbohydrate oxidation rates than the ingestion of a single carbohydrate, attenuating the depletion of endogenous energy stores during exercise and stimulating repletion of these stores during acute post exercise recovery.

    “Moreover, the combination of glucose and fructose have shown to be beneficial since it resulted in higher carbohydrate oxidation rates than the ingestion of a single carbohydrate, attenuating the depletion of endogenous energy stores during exercise and stimulating repletion of these stores during acute post exercise recovery [64].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [64] van Wijck K, 2012, Am J Physiol Gastrointest Liver Physiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    An acute dose of oral glutamine 2 h before intense exercise ameliorates stress-induced intestinal permeability and lowers plasma endotoxins.

    “On the other hand, an acute dose of oral glutamine 2 h before intense exercise ameliorates stress-induced intestinal permeability and lowered plasma endotoxins and may produce anti-inflammatory effects and is a common supplement used to repair and restore intestinal barrier function [122].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [122] Bruunsgaard H, 2000, Immunol Cell Biol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dietary carbohydrate intake ranges from 7 to 12 g/kg per day and fat intake is usually <1 g/kg of body mass per day (<20% of total calories consumed) for athletes who train for more than 2 h/day.

    “Dietary carbohydrate intake ranges from 7 to 12 g/kg per day and fat intake is usually < 1 g/kg of body mass per day (<20% of total calories consumed) for athletes who train for more than 2 h/day [111].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [111] Antonio J, Stout JR, Willoughby D, et al.: Essentials of sports nutrition and supplements. International society of sports nutrition, Human Press 2008

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    High protein diets can affect the microbiota composition and function through amino acid fermentation in the colon that produces undesirable metabolites (e.g. phenol, hydrogen sulfide and amines) and urea and tend to lead to higher fecal pH.

    “While athletes may require a higher protein intake, high protein diets can affect the microbiota composition and function through amino acid fermentation in the colon that produces undesirable metabolites (e.g. phenol, hydrogen sulfide and amines) and urea and tend to lead to higher fecal pH (reviewed by Windey et al [129]).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [129] Windey K, 2012, Mol Nutr Food Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Bifidobacterium longum R0175 can reduce anxiety and free cortisol levels and improve anxiety and depression.

    “Bifidobacterium longum R0175 (PF) can reduce anxiety and free cortisol levels [133].”
    • Also stated in: § Dietary recommendations to reduce the exercise-induced stress behavior and symptoms and to improve the gut microbiota composition and function for athletes · plain
      “Bifidobacterium longum R0175 taken for 30 days reduced anxiety-like behaviors and stress levels (indicated by urinary free cortisol levels), and significant improvements in anxiety and depression were observed [165].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [133] Hughes R, 2000, Curr Issues Intest Microbiol

      Not checked in the free run.

    • cites [165] Messaoudi M, 2011, Gut Microbes source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Diets high in simple and refined carbohydrates do not promote a healthy gut microbiota composition nor produce beneficial SCFA.

    “Nevertheless, diets high in simple and refined carbohydrates do not promote a healthy gut microbiota composition nor do they produce beneficial SCFA [116].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [116] De Filippo C, 2010, Proc Natl Acad Sci U S A source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A high carbohydrate diet does not improve immune function nor prevent decreased plasma glutamine concentrations after heavy periods of training.

    “However, a high carbohydrate diet does not improve immune function nor it does prevent decreased plasma glutamine concentrations after heavy periods of training [105, 113].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [105] Gleeson M, 2008, J Nutr source

      Not checked in the free run.

    • cites [113] Gleeson M, 2000, Immunol Cell Biol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Lactobacillus helveticus reduces plasma ACTH and corticosterone concentrations in response to stress in rats and can restore hippocampal serotonin (5-HT) and NE levels.

    “Lactobacillus helveticus also reduces anxiety [133] and plasma ACTH and corticosterone concentrations in response to stress in rats and can restore hippocampal serotonin (5-HT) and NE levels [74].”
    • Also stated in: § Dietary recommendations to reduce the exercise-induced stress behavior and symptoms and to improve the gut microbiota composition and function for athletes · plain
      “Lactobacillus farciminis and Lactobacillus helveticus NS8 have been shown to decrease plasma ACTH and corticosterone concentrations in response to stress in rats [167, 168], as well as restore hippocampal serotonin and NE levels and decrease neuroinflammation [169].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [74] den Besten G, 2013, J Lipid Res source

      Not checked in the free run.

    • cites [167] Ait-Belgnaoui A, 2012, Psycho Neuro Endocrinol source

      Not checked in the free run.

    • cites [168] Liang S, 2015, Neuroscience source

      Not checked in the free run.

    • cites [169] Ait-Belgnaoui A, 2014, Neuro Gastroenterol Motil source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Diets high in red meat lead to a higher risk in cardiovascular disease due to microbiota-dependent production of TMAO.

    “The authors concluded that diets high in red meat lead to a higher risk in cardiovascular disease due to microbiota-dependent production of TMAO.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [134] Koeth RA, 2013, Nat Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Acetate, propionate and N-butyrate are mediators of the colonic inflammatory response, stimulate sympathetic nervous system and mucosal serotonin release.

    “Acetate, propionate and N-butyrate are mediators of the colonic inflammatory response [154], stimulate sympathetic nervous system [155] and mucosal serotonin release [156].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [154] Del Chierico F, 2014, Intern J Mol Scien source

      Not checked in the free run.

    • cites [155] Kimura I, 2011, Proc Natl Acad Sci USA source

      Not checked in the free run.

    • cites [156] Grider JR, 2007, Am J Physiol Gastrointest Liver Physiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    High dietary casein caused a 2-fold increase in colonic DNA damage compared to a low casein diet and reduced the thickness of the colonic mucus layer by 41% in rats.

    “High dietary casein caused a 2-fold increase in colonic DNA damage compared to a low casein diet and reduced the thickness of the colonic mucus layer by 41%.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [135] Toden S, 2006, Cancer Biol Ther source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    P-cresol, phenols, certain amines and hydrogen sulfide have a known role in irritable bowel disease, colon cancer, increased intestinal permeability, inflammation, DNA damage and more.

    “P-cresol, phenols, certain amines and hydrogen sulfide have a known role in irritable bowel disease, colon cancer, increased intestinal permeability, inflammation, DNA damage and more [36].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Marchesi JR, 2016, Gut source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Fat consumption among athletes tends to be quite low, comprising between 15-30% of the dietary energy.

    “Fat consumption among athletes tends to be quite low, comprising between 15-30% of the dietary energy [139].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [139] Williams C, 1997, World Rev Nutr Diet

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Consuming probiotics regularly may positively modify the gut microbiota's population and structure and may influence immune function as well as intestinal epithelium cell proliferation, function and protection in individuals who follow exercise.

    “There is now a reasonable body of evidence that shows that consuming probiotics regularly may positively modify the gut microbiota’s population and structure and may influence immune function as well as intestinal epithelium cell proliferation, function and protection in individuals who follows exercise (reviewed by Mach et al [23]).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] Mach N and Fuster-Botella D: Endurance exercise and gut microbiota: A review. J Sport Health Sci 2016 (In press). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In tumor-bearing mice, NK cell infiltration was significantly increased in tumors from running mice, whereas depletion of NK cells enhanced tumor growth and blunted the beneficial effects of exercise.

    “Little is known about the mechanisms behind NK protection during exercise, but very recently, Pedersen et al [145] have demonstrated in tumor-bearing mice that NK cell infiltration was significantly increased in tumors from running mice, whereas depletion of NK cells enhanced tumor growth and blunted the beneficial effects of exercise.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [145] Pedersen L, 2016, Cell Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Omega-6 polyunsaturated fatty acids can alter cell membrane fluidity and indirectly affect immune function including reduced IL2 production and suppressed mitogen-induced lymphocyte proliferation.

    “Omega-6 polyunsaturated fatty acids can alter cell membrane fluidity and indirectly affect immune function including reduced IL2 production and suppressed mitogen-induced lymphocyte proliferation producing potentially an undesirable immune function during and after exercise [146].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [146] Konig D, 1997, Exerc Immunol Rev

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    High levels of cooked meat caused 26% greater DNA damage than the high casein diet but reduced mucus thickness to a similar degree to casein in rats.

    “High levels of cooked meat caused 26% greater DNA damage than the high casein diet but reduced mucus thickness to a similar degree to casein [135].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [135] Toden S, 2006, Cancer Biol Ther source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NK cell activity increased in the group that had the carbohydrate-rich diet [from 16% to 27%] and decreased in the group that had the fat-rich diet [from 26% to 20%] in response to training.

    “NK cell activity had increased in the group that had the carbohydrate-rich diet [from 16% to 27%] and decreased in the group that had the fat-rich diet [from 26% to 20%] in response to training [144].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [144] Pedersen BK, 2000, Eur J Appl Physiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Consumption of diets high in fat and calories is associated with chronic low-grade systemic inflammation, increased intestinal permeability and plasma LPS together with a decrease in total bacterial density and an increase in the relative proportion of Bacteroidales and Clostridiales orders.

    “On top of that, consumption of diets high in fat and calories is associated with chronic “low-grade” systemic inflammation, increased intestinal permeability and plasma LPS together with a decrease in total bacterial density and an increase in the relative proportion of Bacteroidales and Clostridiales orders [149].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [149] de La Serre CB, 2010, Am J Physiol Gastrointest Liver Physiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A high-fat diet can lead to increased anxiety-like behavior with selective disruptions in exploratory, cognitive, and stereotypical behavior, neuroinflammation, disrupted markers of intestinal barrier function, as well as increased circulating endotoxin and lymphocyte expression compared to mice with control diet.

    “On the other hand, high-fat diet can lead to increased anxiety-like behavior with selective disruptions in exploratory, cognitive, and stereotypical behavior, neuroinflammation disrupted markers of intestinal barrier function, as well as increased circulating endotoxin and lymphocyte expression compared to mice with control diet [143].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [143] Bruce-Keller AJ, 2015, Biol Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In Wistar rats, 14-day administration of combined Lactobacillus helveticus and Bifidobacterium longum reduced anxiety-like behavior in the defensive marble burying test possibly because the probiotic reduced HPA acids and ANS activity.

    “In Wistar rats, 14-day administration of combined Lactobacillus helveticus and Bifidobacterium longum reduced anxiety-like behavior in the defensive marble burying test possibly because the probiotic reduced HPA acids and ANS activity [165].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [165] Messaoudi M, 2011, Gut Microbes source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    An increase in fat metabolism (30-50% dietary energy) during prolonged exercise may have a glycogen sparing effect and may improve endurance performance and health.

    “An increase in fat metabolism (30-50% dietary energy) during prolonged exercise may have a glycogen sparing effect and may improve endurance performance [140] and health [141].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [140] Bjorntorp P, 1991, J Sports Sci source

      Not checked in the free run.

    • cites [141] Pendergast DR, 2000, J Am College Nutr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Gut microbiota from mice supplemented with L-carnitine had an altered cecum microbiota composition that metabolized trimethylamine into trimethylamine-N-oxide (TMAO), which is associated with atherosclerosis.

    “Koeth et al [134] reported the gut microbiota from mice that were supplemented with L-carnitine had an altered cecum microbiota composition that metabolized trimethylamine into trimethylamine-N-oxide (TMAO), which is associated with atherosclerosis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [134] Koeth RA, 2013, Nat Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    NK cells represent a critical component of the innate immune defense, recognizing transformed cells independently of antibodies or major histocompatibility complex restriction.

    “NK cells represent a critical component of the innate immune defense, recognizing transformed cells independently of antibodies or major histocompatibility complex restriction [145].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [145] Pedersen L, 2016, Cell Metab source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    The gut microbiota has fundamental roles in many aspects of human biology, including metabolism, endocrine, neuronal and immune function.

    “The gut microbiota has fundamental roles in many aspects of human biology, including metabolism, endocrine, neuronal and immune function.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Lactobacillus farciminis and Lactobacillus helveticus NS8 have been shown to decrease plasma ACTH and corticosterone concentrations in response to stress in rats, as well as restore hippocampal serotonin and NE levels and decrease neuroinflammation.

    “Lactobacillus farciminis and Lactobacillus helveticus NS8 have been shown to decrease plasma ACTH and corticosterone concentrations in response to stress in rats [167, 168], as well as restore hippocampal serotonin and NE levels and decrease neuroinflammation [169].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [167] Ait-Belgnaoui A, 2012, Psycho Neuro Endocrinol source

      Not checked in the free run.

    • cites [168] Liang S, 2015, Neuroscience source

      Not checked in the free run.

    • cites [169] Ait-Belgnaoui A, 2014, Neuro Gastroenterol Motil source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    The gut and the microbiota are important organs for athletic performance because they are responsible for the delivery of water, nutrients and hormones during exercise.

    “The gut and the microbiota are important organs for athletic performance because they are responsible for the delivery of water, nutrients and hormones during exercise.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Supplementing the diet with prebiotics and/or probiotics that stimulate the expansion of specific microorganisms such as Bifidobacteria and Lactobacillus and beneficial metabolites such as SCFA can improve metabolic, immune and barrier function and can be a therapy for athletes.

    “Supplementing the diet with prebiotics and/or probiotics that stimulate the expansion of specific microorganisms such as Bifidobacteria and Lactobacillus and beneficial metabolites such as SCFA to improve the metabolic, immune and barrier function can be a therapy for athletes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Exercise-induced stress modifies stress and catabolic hormones, cytokines and gut microbial molecules, which might result in gastrointestinal disturbances, anxiety, depression, and underperformance.

    “Exercise-induced stress modifies stress and catabolic hormones, cytokines and gut microbial molecules, which might result in gastrointestinal disturbances, anxiety, depression, and underperformance.”
    Quote in the paperSubstantial claim
125 of 125

  • The paper relies on this without support.

    Findings from murine models on exercise-induced stress and gut microbiota can be generalised to human athletes.

    “Recent evidence in murine models shows that there is a high correlation between physical and emotional stress during exercise and changes in gastrointestinal microbiota composition.”

  • The paper relies on this without support.

    The relationship between exercise-induced stress and gut microbiota composition, and the possible pathophysiological mechanisms involved, has not yet been explored.

    “However, beyond those functions, we noted that the relationship between exercise-induced stress and gut microbiota composition, as well as the possible pathophysiological mechanisms involved has not yet been explored.”

  • The paper relies on this without support.

    The role of microbiota in controlling exercise-induced stress adaptation remains unknown.

    “However, the role of microbiota in controlling exercise-induced stress adaptation remains unknown.”

  • The authors state this as an assumption.

    Each dietary plan is probably accompanied by a simultaneous adjustment of the microbiota.

    “It can be assumed that each dietary plan is probably accompanied by a simultaneous adjustment of the microbiota [112].”

  • The paper relies on this without support.

    Findings from rodent studies on exercise, gut microbiota, SCFA and neurotransmitters can be generalized to human athletes.

    “Matsumoto et al [80] performed a study in 14 male Wistar rats during five weeks.”
    “Desbonnet et al [107] administered the probiotic strain Bifidobacterium infantis during 14 days in naive rats who performed a forced swim test.”

  • The paper relies on this without support.

    The human microbiome is highly diverse.

    “Due to the great diversity of the human microbiome, there have not been specific established dietary recommendations for probiotic supplementation for athletes.”

  • The paper relies on this without support.

    Probiotic supplementation is highly variable depending on the strain, microbial composition and metagenome.

    “Probiotic supplementation is highly variable depending on the strain, microbial composition and metagenome.”

  • The paper relies on this without support.

    BCAA compete with free tryptophan to cross the blood–brain barrier.

    “While BCAA do compete with free tryptophan to cross the blood–brain barrier, evidence that increased brain 5-HTP is driven by an increase in free tryptophan pools in blood is very weak.”
8 of 8

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The gut microbiota acts as an endocrine organ, secreting neurotransmitters such as serotonin and dopamine, thereby controlling the hypothalamic-pituitary axis in athletes.

    “These authors concluded that the gut microbiota acts as an endocrine organ, secreting neurotransmitters such as serotonin and dopamine, thereby controlling the hypothalamic-pituitary axis in athletes.”

    From International Society of Sports Nutrition Position Stand: Probiotics (2019) · cites this paper as [280]

  • The gut microbiota, with its ability to harvest energy, modulate the immune system, and influence gastrointestinal and brain health, likely plays a significant role in athlete health, wellbeing, and sports performance.

    “In addition, the gut microbiota with its ability to harvest energy, modulate the immune system, and influence gastrointestinal health, likely plays an important role in athlete health, wellbeing, and sports performance.”

    From The athletic gut microbiota (2020) · cites this paper as [15]

  • Many athletes may not be consuming enough fiber to feed commensal bacteria that produce beneficial byproducts for host metabolism and homeostasis.

    “Many athletes may not be consuming enough fiber that feed commensal bacteria that produce beneficial byproducts for host metabolism and homeostasis [15].”

    From The athletic gut microbiota (2020) · cites this paper as [15]

  • Modulation of the gut microbiota reduces systemic inflammation and sympathetic nervous system activity, both of which contribute to hypertension and chronic kidney disease.

    “Modulation of the gut microbiota reduces systemic inflammation and SNS activity, both of which contribute to hypertension and CKD80,162,208.”

    From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [208]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Direction of Turicibacter change is reversed

    Major

    The conclusion says intense exercise-induced stress decreased Turicibacter, but the described study found lower levels in voluntary runners than in forced treadmill runners. The study description therefore reports the opposite direction for the stressed group.

  • Exercise-microbiota relationship described as both unexplored and studied

    Minor

    The background says the relationship between exercise-induced stress and microbiota composition has not yet been explored, whereas the main text identifies a study directly examining it.

  • IDO and TDO said to both promote and reduce serotonin synthesis

    Minor

    The text first presents the IDO- and TDO-regulated kynurenine pathway as a route for serotonin production, then says induction of those enzymes leads to less serotonin synthesis.

  • Higher-fat diet labeled low-fat

    Minor

    The diet labeled "low-fat" has 36.5% of calories from fat, more than twice the 15.4% in the diet labeled "moderate-fat."

4 of 4

Cites

Flagged first, then by citations

4 of the 173 references couldn’t be matched to a known paper.

Research works printed but not linked: 15

  1. Carabotti M, 2015, Ann Gastroenterol, 28, 203
  2. Heijnen S, 2015, Front Psychol, 6, 1890
  3. Foster J, 2015, Europ Neuro Psycho Pharmacol, 25, 14
  4. Bermon S, 2015, Exerc Immunol Rev, 21, 70
  5. Brock-Utne JG, 1988, S Afr Med J, 73, 533
  6. Puddu A, 2014, Mediators Inflamm, 2014, 1
  7. Gleeson M, 2007, J Appl Physiol, 103, 693, 10.1152/japplphysiol.00008.2007 · DOI · Paper page
  8. Otsuka T, 2016, Beh Brain Res, 1, 44, 10.1016/j.bbr.2015.10.055 · DOI · Paper page
  9. van Wijck K, 2012, Am J Physiol Gastroint Liver Physiol, 303, 155, 10.1152/ajpgi.00066.2012 · DOI · Paper page
  10. Drygas W, 2014, J Sports Sci Med, 13, 632
  11. Hughes R, 2000, Curr Issues Intest Microbiol, 1, 51
  12. Williams C, 1997, World Rev Nutr Diet, 82, 33
  13. Konig D, 1997, Exerc Immunol Rev, 3, 1
  14. Caccialanza R, 2007, J Sports Sci Med, 6, 538
  15. de Oliveira EP, 2014, Sports Med, 44, 79, 10.1007/s40279-014-0153-2 · DOI · Paper page

Cited by

Sorted by citations

Related

Authors
Clark, A., & Mach, N.
Affiliations
Universitat Oberta de Catalunya (ES)
Corresponding author
Mach, Núria
ORCID
Mach, Núria
Venue
Journal of the International Society of Sports Nutrition
Publisher
Informa UK Limited
Published
2016-01-05
Volume
13
Issue
1
Pages
43-43
ISSN
1550-2783 (ISSN-L)
DOI
10.1186/s12970-016-0155-6
PMC
PMC5121944
OpenAlex
W2552747592
Semantic Scholar
17a154a4ec1298ecd0083d3adb8ce109d5f0a296
Cited by
583
References
173
Citations by year
2026: 50 · 2025: 76 · 2024: 91 · 2023: 91 · 2022: 76 · 2021: 61 · 2020: 40 · 2019: 43 · 2018: 33 · 2017: 21 · 2015: 1
FWCI
2.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the International Society of Sports Nutrition (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
  • The Oberta in Open Access (Universitat Oberta de Catalunya) (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
exercise stress, gut microbiota, gut-brain axis, athletes, hypothalamic-pituitary-adrenal axis, dietary fiber, probiotics, prebiotics, short-chain fatty acids, gastrointestinal distress, fatigue, mood disturbance, Turicibacter, Ruminococcus gnavus, plant polysaccharides, microbial metabolites
MeSH terms
Gastrointestinal Microbiome, Brain, Diet, Food, Hormones, Humans, Stress, Psychological, Probiotics, Gastrointestinal Tract, Athletic Performance, Athletes, Sports Nutritional Physiological Phenomena

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-08.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-08.

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