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

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.

Keywords: Athlete; Behaviour; Diet; Exercise; Microbiota; Neurotransmitters; Stress.

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 [V_O2max]) before circulating levels increase in response to exercise [170, 171]

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. 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.