Mechanisms by which Stress Affects the Experimental and Clinical Inflammatory Bowel Disease (IBD): Role of Brain-Gut Axis

Abstract

Background: Stress of different origin is known to alter so called "braingut axis" and contributes to a broad array of gastrointestinal disorders including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other functional gastrointestinal diseases. The stressful situations and various stressors including psychosocial events, heat, hypo- and hyperthermia may worsen the course of IBD via unknown mechanism. The aims of this paper were to provide an overview of experimental and clinical evidences that stress activates the brain-gut axis which results in a mucosal mast cells activation and an increase in the production of proinflammatory cytokines and other endocrine and humoral mediators.

Methods: Research and online content related to effects of stress on lower bowel disorders are reviewed and most important mechanisms are delineated.

Results: Brain conveys the neural, endocrine and circulatory messages to the gut via brain-gut axis reflecting changes in corticotrophin releasing hormone, mast cells activity, neurotransmission at the autonomic nerves system and intestinal barrier function all affecting the pathogenesis of animal colitis and human IBD. Stress triggers the hypothalamus-pituitary axis and the activation of the autonomic nervous system, an increase in cortisol levels and proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-8, interleukin-1beta and interleukin-6.

Conclusion: The acute or chronic stress enhances the intestinal permeability weakening of the tight junctions and increasing bacterial translocation into the intestinal wall. An increased microbial load in the colonic tissue, excessive cytokine release and a partially blunted immune reactivity in response to stress result in its negative impact on IBD.

Fig. (1)

The complexity of stress affecting the function of brain, gut intestinal mucosa and particular functional components of intestinal wall via brain-gut axis. In response to stress, the inflammatory cytokines (TNF-α), various chemicals, short chain fatty acids (SCFA), and microbial products can alter the autonomic nervous system (ANS) leading to secretion of cortisol and adrenaline from adrenals via CRF of and ACTH-dependent pathways. The gut microbiota and neuroactive chemicals including histamine released from mast cells and serotonin (5-hydroxytryptamine) are known to impair the intestinal secretion and intestinal mucosa in response to stress. Various stressors render the intestinal mucosa more permeable, more absorbable to bacterial cytotoxins and neurotransmitters (norepinephrine), and contribute to the development of local inflammation. In conditions associated with stress, bacteria can undergo translocation from intestinal lumen into systemic circulation affecting the central and peripheral organs.

Fig. (2)

Schematic presentation of psychoneurological, endocrine, and immune responses to stress leading to intestinal inflammation, dysbiosis, and functional gastrointestinal disorders (FGIDs) including inflammatory bowel disease (IBD). Stress-induced activation of brain-gut axis and both autonomic and enteric systems (ANS and ENS) causes intestinal inflammation mediated by degranulation of mast cells releasing histamine and proinflammatory cytokines, T lymphocyte cell activation and bacterial translocation from mucosa to blood stream and peripheral organs.