title: Maladaptive intestinal epithelial responses to life stress may predispose healthy women to gut mucosal inflammation.
abstract: OBJECTIVE
  Irritable bowel syndrome (IBS), a highly prevalent disorder among women, has been associated with life stress, but the peripheral mechanisms involved remain largely unexplored.
  
  
  METHODS
  A 20-cm jejunal segment perfusion was performed in 2 groups of young healthy women, equilibrated by menstrual phase, experiencing either low (LS; n = 13) or moderate background stress (MS; n = 11). Intestinal effluents were collected every 15 minutes, for 30 minutes under basal conditions, and for 1 hour after cold pain stress. Cardiovascular and psychological response, changes in circulating stress and gonadal hormones, and epithelial function (net water flux, albumin output and luminal release of tryptase and alpha-defensins) to cold stress were determined.
  
  
  RESULTS
  Cold pain induced a psychological response stronger in the MS than in the LS group, but similar increases in heart rate, blood pressure, adrenocorticotrophic hormone, and cortisol, whereas estradiol and progesterone remained unaltered. Notably, the jejunal epithelium of MS females showed a chloride-related decrease in peak secretory response (Delta[15-0 minutes]: LS, 97.5 [68.4-135.0]; MS, 48.8 [36.6-65.0] microL/min/cm; P < .001) combined with a marked enhancement of albumin permeability (LS(AUC), 6.35 [0.9-9.6]; MS(AUC), 13.97 [8.3-23.1] mg/60 min; P = .008) after cold stress. Epithelial response in both groups was associated with similar increases in luminal tryptase and alpha-defensins release.
  
  
  CONCLUSIONS
  Increased exposure to life events determines a defective jejunal epithelial response to incoming stimuli. This abnormal response may represent an initial step in the development of prolonged mucosal dysfunction, a finding that could be linked to enhanced susceptibility for IBS.
authors.affiliation: Digestive Diseases Research Unit, Institut de Reçerca, Department of Gastroenterology, Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Alonso
authors.forename: Mar
authors.initials: M
authors.lastname: Guilarte
authors.forename: Maria
authors.initials: M
authors.lastname: Vicario
authors.forename: Laura
authors.initials: L
authors.lastname: Ramos
authors.forename: Ziad
authors.initials: Z
authors.lastname: Ramadan
authors.forename: Maria
authors.initials: M
authors.lastname: Antolín
authors.forename: Cristina
authors.initials: C
authors.lastname: Martínez
authors.forename: Serge
authors.initials: S
authors.lastname: Rezzi
authors.forename: Esteban
authors.initials: E
authors.lastname: Saperas
authors.forename: Sunil
authors.initials: S
authors.lastname: Kochhar
authors.forename: Javier
authors.initials: J
authors.lastname: Santos
authors.forename: Juan Ramón
authors.initials: JR
authors.lastname: Malagelada
mesh_terms: D000328:Adult; D001341:Autonomic Nervous System / Q000502:physiology; D003080:Cold Temperature; D003863:Depression / Q000453:epidemiology / Q000276:immunology / Q000523:psychology; D004751:Enteritis / Q000453:epidemiology / Q000276:immunology* / Q000523:psychology*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000276:immunology; D043183:Irritable Bowel Syndrome / Q000453:epidemiology / Q000276:immunology* / Q000523:psychology*; D007583:Jejunum / Q000201:enzymology / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D008597:Menstrual Cycle; D015213:Neuroimmunomodulation / Q000502:physiology; D010146:Pain / Q000453:epidemiology / Q000276:immunology / Q000523:psychology; D012307:Risk Factors; D013315:Stress, Psychological / Q000453:epidemiology / Q000276:immunology* / Q000523:psychology; D053802:Tryptases / Q000378:metabolism
chemical_list: D053802:Tryptases