Gastroenterology

Gastroenterology

Volume 135, Issue 1, July 2008, Pages 163-172.e1
Gastroenterology

Basic—Alimentary Tract
Maladaptive Intestinal Epithelial Responses to Life Stress May Predispose Healthy Women to Gut Mucosal Inflammation

https://doi.org/10.1053/j.gastro.2008.03.036Get rights and content

Background & Aims: 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 α-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 (Δ[15-0 minutes]: LS, 97.5 [68.4–135.0]; MS, 48.8 [36.6–65.0] μL/min/cm; P < .001) combined with a marked enhancement of albumin permeability (LSAUC, 6.35 [0.9–9.6]; MSAUC, 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 α-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.

Section snippets

Participants

Fertile female healthy volunteers were prospectively recruited by public advertising. The study protocol was approved by the Ethics Committee at Hospital Vall d'Hebron. Written informed consent was obtained from each participant.

Candidates gave a full medical history and underwent physical examination. Previous gastrointestinal disorders were excluded by anamnesis and Rome II criteria for functional dyspepsia25 and IBS.26 Food and respiratory allergy was ruled out using a battery of skin prick

Demographics, Baseline Stress, and Depression Levels

Thirty-one women were initially recruited. Seven participants were excluded owing to inadequate placing of the tube (n = 2), unacceptable PEG recovery (n = 3), or because menstrual cycle did not match required stress levels to equilibrate subgroups (n = 2). Twenty-four studies were considered evaluable, with no demographic, clinical or menstrual differences between LS and MS groups, other than stress and depression levels (Table 1,Supplementary Figures 1 and 2; see supplementary material online

Discussion

Increasing interest has emerged to understand and explore women's excess risk to develop chronic pain and inflammatory and functional disorders.2 Concerning IBS, attention has been focused on mechanisms involved in gender-based differences in pain modulation33 at the central level with reports showing enhanced viscerosensory perception to colorectal distension34 and greater activation of limbic and paralimbic regions that might be part of a pain-facilitating circuit.35 However, little attention

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    • Cited by (0)

    Supported in part by Nestec S. A. and the Spanish Ministry of Sanidad y Consumo, Subdirección General de Investigación Sanitaria, Instituto Carlos III, Fondo de Investigación Sanitaria. Dr C. Alonso (CM04/00019), Dr Laura Ramos (CM05/00055), Dr Maria Vicario (CD05/00060) and Dr J. Santos (F.I.S. 05/1423) were the recipients of these grants.

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