New Insights in the Etiology and Pathophysiology of Irritable Bowel Syndrome: Contribution of Neonatal Stress Models

Abstract

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, characterized by abdominal pain and disturbed defecation that cannot be explained by structural abnormalities. Although IBS symptoms (visceral pain, increased gut permeability, motility alterations) are clearly established, the etiology of this pathology is loosely understood. Nevertheless, clinical studies have reported that some early abuse (physical and psychological) is often associated with IBS development. Thus, loss and separation in the family during childhood may contribute to the IBS development. The recent development of animal models has pointed out the importance of early traumatic experiences in favoring the occurrence of IBS in adult life. Among these different models, neonatal maternal deprivation (NMD), neonatal colonic irritation (inflammatory stimuli), and neonatal colonic pain (rectal distension) have been described to mimic some cardinal features of IBS. The purpose of this review is 3-fold. First, to present the different neonatal stress models. Second, to review the literature on the influence of these early traumatic experiences on the gastrointestinal tract disturbances observed in adult life. Finally, we will also present the mediators and mechanisms involved in gut dysfunction triggered by NMD and probably in IBS. (Pediatr Res 62: 240-245, 2007)

Maternal Separation Induced Visceral Hypersensitivity from Childhood to Adulthood

“…In a variety of stress related IBS models, MS of newborn rats is considered to be a well-established model of early life stress induced visceral hypersensitivity. 7 In 2002, Coutinho et al 5 showed that maternal separated Long-Evans rats suffered from stressinduced visceral hyperalgesia and increased colonic motility, which could mimic IBS in humans. To date, accumulating animal experiments 16 confirm that neonatal MS could induce visceral hyperalgesia in adult rats, suggesting early life adverse events can strengthen neural responses to visceral nociceptive stimulus in 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.…”

“…Several studies indicated that disturbed gastrointestinal motility, visceral hypersensitivity, immune dysregulation and mucosal barrier dysfunction are thought to be involved in the development of EALs-related IBS. [5][6][7][8][9] Visceral hypersensitivity is one important pathophysiological mechanism in the generation of IBS. 10,11 Many previous experimental studies found that EALs such as maternal separation (MS) can induce adult visceral hypersensitivity.…”

“…5 MS in rodents could well mimic EALs in humans and the MS model was commonly used to explore the underlying mechanism of EALs related IBS in many studies. 6,7 Based on the MS rat model, this research aims to explore the effect of MS on visceral sensitivity and anxiety-like behavior in the different age stages of rats, and expect to provide a basis for further exploration of the mechanisms of EALs induced IBS.…”

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

“…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.…”