Pathophysiological Mechanisms of Stress-Induced Intestina Damage

Abstract

Stress has been shown to have both central and peripheral effects, promoting psychological illness (such as anxiety and depression), as well influencing peripheral disease in the intestine. Stress in humans can exacerbate symptoms of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), lowering visceral pain thresholds and decreasing mucosal barrier function. Studies in rodents have revealed that both acute and chronic exposure to stressors can lead to pathophysiology of the small and large intestine, including altered ion secretion and increased epithelial permeability (by both transcellular and paracellular pathways). Prolonged exposure to stress can induce low-grade inflammation, cause ultrastructural epithelial abnormalities, and alter bacterial-host interactions allowing greater microbial translocation. In this review, we discuss the stress response and the effects of both acute and chronic stress to induce pathophysiological damage to the gut. We present the potential pathways involved, and the proposed mechanisms of action mediating the effects. Furthermore, we explore the impact of early life stress on colonic physiology in neonatal rodents and the implications for gut dysfunction in adulthood.

Chronic Early-life Stress in Rat Pups Alters Basal Corticosterone, Intestinal Permeability, and Fecal Microbiota at Weaning: Influence of Sex

“…Other studies performed in male rats indicate an alteration of the intestinal barrier at weaning in the maternal separation model 23 that was detected by the significant increase of colonic short-circuit current and horseradish peroxidase flux along with increased intestinal permeability that was still maintained in adulthood. 6,34 Glucocorticoids play a role in the increased intestinal permeability induced by a short acute maternal separation stress in PND10 pups 17 but not in adult rats subjected to repeated maternal separation. 36,37 In the present study, we found no correlation between corticosterone plasma levels and intestinal permeability at weaning, either in LNS or BMS models, suggesting that glucocorticoids are not involved in the mechanisms contributing to the altered permeability.…”

“…1,2 In preclinical studies, rodents raised under conditions of intermittent maternal separation develop features of IBS-like manifestations and alterations in behavior when they are adults. [3][4][5][6] Another model of early-life adverse events is the rearing of pups by dams subjected postpartum to conditions of limited bedding and nesting stress. 7,8 This model has face validity in humans 7,8 where the mother is continuously present but provides an altered repertoire of maternal behaviors indicative of fragmented and erratic care 9 and altered dam-pup interactions.…”

Maternal Separation Induced Visceral Hypersensitivity from Childhood to Adulthood

“…23,24 Animal studies also found that early life stressful events such as MS in the rodent can cause disruption of the HPA axis. 7,25,26 Early life stress can influence development of the HPA axis, as well as regulation of satiety-related hormones, leptin, insulin, and ghrelin, again influencing appetite, feeding behavior, and metabolism, which results in the development of obesity. 27 The weight of MS rats can gradually return to normal level on PND56, suggesting that the harmful effect of MS on weight can be improved in rat adulthood after normal feeding.…”

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

“…Inflammatory cytokines and the vagal system in turn can modulate the activity of the CNS and ENS. 38,39 Furthermore, increased permeability of the gut can also increase the translocation of metabolic products such as lipopolysaccharide (LPS) or neuroactive peptides created by the bacteria that can alter the activity of the ENS and CNS. 40 For example, LPS can activate Toll-Like receptors that are present on epithelial cells, enteric neurons, sensory afferent neurons in the spine, and various cells in the brain, modulating their activity and affecting the function of both ENS and CNS.…”