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

The DOI matches its Crossref record; 169 of the 173 references it cites were found in a registry or an index; 5 of the 267 sources its claims cite were checked for support.

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

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.

Overview

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.

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Integrity signals

Registry

Crossref · 10.1186/s12970-016-0155-6

Cites

169 of 169 references verified0 citation errors · 0 not checkable

Statistics

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Figures

Fig. 1 Stress hormones released during high intense exercise. Stress responses to intense exercise are mediated by largely overlapping circuits in the limbic forebrain, the hypothalamus and the brainstem, so that the respective contributions on the neuroendocrine and autonomic systems are tuned in accordance with stressor and intensity [6]. When brainstem receives inputs that signal major homeostatic perturbations, such as respiratory distress, energy imbalance, desydration, visceral or somatic pain, inflammation or exteroceptive factors respond through a coordinated modulation of the HPA axis and the sympathetic and parasympathetic branch of the autonomic nervous system (ANS). By contrast, forebrain limbic regions have no direct connections with the HPA axis or the ANS and thus require intervening synapses before they can access autonomic or neuroendocrine neurons (top-down regulation) [6]. 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. Parasympathetic tone can also be modulated during stress (shown in dark grey color). Parasympathetic actions are generally opposite to those of the sympathetic system and alter the vagal tone to the heart and lungs. 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), which in turn acts on the inner adrenal cortex to initiate the synthesis and release of glucocorticoid hormones. Moreover, the adrenal cortex is directly innervated by the sympathetic nervous system, which can also regulate corticosteroid release. Additionally, gastrointestinal tract responds to stress in an endocrine manner by releasing hormones such as Gamma-amino butyric acid (GABA), neuropeptide Y and dopamine that have been purported to be involved in the gastrointestinal disturbances, anxiety, depression, reduced food intake and less stress coping. 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. The neuroendocrine stress response to exercise is determined not only by the emotional stress but the volume of physical exposure, where volume consists of the intensity and/or duration of the exercise session. As exercise intensity is increased, there are approximately proportional increases in circulating concentrations of ACTH and cortisol. There is a critical threshold of exercise intensity that must be reached (~50–60% of maximal oxygen uptake [VO2max]) before circulating levels increase in response to exercise [170, 171]
Fig. 1 Stress hormones released during high intense exercise. Stress responses to intense exercise are mediated by largely overlapping circuits in the limbic forebrain, the hypothalamus and the brainstem, so that the respective contributions on the neuroendocrine and autonomic systems are tuned in accordance with stressor and intensity [6]. When brainstem receives inputs that signal major homeostatic perturbations, such as respiratory distress, energy imbalance, desydration, visceral or somatic pain, inflammation or exteroceptive factors respond through a coordinated modulation of the HPA axis and the sympathetic and parasympathetic branch of the autonomic nervous system (ANS). By contrast, forebrain limbic regions have no direct connections with the HPA axis or the ANS and thus require intervening synapses before they can access autonomic or neuroendocrine neurons (top-down regulation) [6]. 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. Parasympathetic tone can also be modulated during stress (shown in dark grey color). Parasympathetic actions are generally opposite to those of the sympathetic system and alter the vagal tone to the heart and lungs. 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), which in turn acts on the inner adrenal cortex to initiate the synthesis and release of glucocorticoid hormones. Moreover, the adrenal cortex is directly innervated by the sympathetic nervous system, which can also regulate corticosteroid release. Additionally, gastrointestinal tract responds to stress in an endocrine manner by releasing hormones such as Gamma-amino butyric acid (GABA), neuropeptide Y and dopamine that have been purported to be involved in the gastrointestinal disturbances, anxiety, depression, reduced food intake and less stress coping. 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. The neuroendocrine stress response to exercise is determined not only by the emotional stress but the volume of physical exposure, where volume consists of the intensity and/or duration of the exercise session. As exercise intensity is increased, there are approximately proportional increases in circulating concentrations of ACTH and cortisol. There is a critical threshold of exercise intensity that must be reached (~50–60% of maximal oxygen uptake [VO2max]) before circulating levels increase in response to exercise [170, 171]CC BY · PubMed Central
Fig. 2 Gastrointestinal disruption during high intensity exercise. Proper intestinal barrier function is crucial for maintaining health and immunity. 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]. 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]. 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. Additionally, intestinal permeability may be made worse by the increased production of reactive oxygen species (ROS) and by the alteration of gut-microbiota composition and activity (the so-called dysbiosis). Furthermore, gastrointestinal tract responds to stress by releasing hormones such as GABA, neuropeptide Y (NPY) and dopamine that have been purported to cause GI disturbances, anxiety, depression, reduced food intake and less stress coping [9]. Conversely, the microbiota’s production of butyrate and propionate can increase transepithelial resistance, which improves intestinal barrier function and decreases inflammation.
Fig. 2 Gastrointestinal disruption during high intensity exercise. Proper intestinal barrier function is crucial for maintaining health and immunity. 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]. 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]. 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. Additionally, intestinal permeability may be made worse by the increased production of reactive oxygen species (ROS) and by the alteration of gut-microbiota composition and activity (the so-called dysbiosis). Furthermore, gastrointestinal tract responds to stress by releasing hormones such as GABA, neuropeptide Y (NPY) and dopamine that have been purported to cause GI disturbances, anxiety, depression, reduced food intake and less stress coping [9]. Conversely, the microbiota’s production of butyrate and propionate can increase transepithelial resistance, which improves intestinal barrier function and decreases inflammation.CC BY · PubMed Central
Fig. 3 Gut microbiota effects on mood disturbance, fatigue, insomnia and risk of depression during exercise. The putative mechanisms by which bacteria connects with the brain and influence behavior during exercise include bacterial subproducts that gain access to the brain via the bloodstream and the area postrema, via cytokine release from mucosal immune cells, via the release of gut hormones such as 5-hydroxytryptamine (5-HT) from enteroendocrine cells, or via afferent neural pathways, including the vagus nerve. Stress during intense period of training and competitions can influence the microbial composition of the gut through the release of stress hormones or sympathetic neurotransmitters that influence gut physiology and alter the habitat of the microbiota (reviewed by Mach [23]). Alternatively, host stress hormones such as noradrenaline might influence bacterial gene expression or signaling between bacteria, and this might change the microbial composition and activity of the microbiota.
Fig. 3 Gut microbiota effects on mood disturbance, fatigue, insomnia and risk of depression during exercise. The putative mechanisms by which bacteria connects with the brain and influence behavior during exercise include bacterial subproducts that gain access to the brain via the bloodstream and the area postrema, via cytokine release from mucosal immune cells, via the release of gut hormones such as 5-hydroxytryptamine (5-HT) from enteroendocrine cells, or via afferent neural pathways, including the vagus nerve. Stress during intense period of training and competitions can influence the microbial composition of the gut through the release of stress hormones or sympathetic neurotransmitters that influence gut physiology and alter the habitat of the microbiota (reviewed by Mach [23]). Alternatively, host stress hormones such as noradrenaline might influence bacterial gene expression or signaling between bacteria, and this might change the microbial composition and activity of the microbiota.CC BY · PubMed Central

Verification

Claims the paper makes

211 Not checked yet · 16 Own interpretation · 13 No basis given · 3 Partly supported · 1 Supported · accuracy not yet measured

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Show all 119 claims

  • It may state two separate claims as one. 104
  • Probably not a substantial claim. 32
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.”
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Citations

Cites

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
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  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

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Metadata

Authors
Clark, A., & Mach, N.
Affiliations
Universitat Oberta de Catalunya (ES)
Corresponding author
Mach, Núria
Venue
Journal of the International Society of Sports Nutrition
Published
2016-01-05
Volume
13
Issue
1
Pages
43-43
ISSN
1550-2783 (ISSN-L)
OpenAlex
W2552747592
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
FWCI
2.92
Type
journal article
Language
en
Open access
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

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