Early life stress triggers persistent colonic barrier dysfunction and exacerbates colitis in adult IL-10-/- Mice

E. M. Lennon*, Nitsan Maharshak, H. Elloumi, L. Borst, S. E. Plevy, Adam J. Moeser

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Background: It has become increasingly evident that disease flares in the human inflammatory bowel diseases are influenced by life stress. It is known that life stress can trigger disturbances in intestinal barrier function and activate proinflammatory signaling pathways, which are important contributors to intestinal inflammation and clinical disease; however, the exact mechanisms of stress-induced inflammatory bowel disease exacerbations remain to be elucidated. Here, we presented a model of early life stress-induced exacerbation of colitis in interleukin (IL)-10-/- mice. Methods: C57Bl/6 wild-type and IL-10-/- mice were exposed to neonatal maternal separation (NMS) stress on postnatal days 1 to 18 and reared under normal conditions until 10 to 12 weeks of age. At this time, histopathology, colitis scores, intestinal barrier function, proinflammatory cytokine expression, and mast cell activity were evaluated. Results: NMS increased the severity of colitis IL-10 -/- mice indicated by greater colitis scores and colonic proinflammatory cytokine concentrations. NMS and IL-10-/- increased colonic permeability; however, NMS alone did not induce colitis. Increased mast cell activation and colonic tryptase release were observed in IL-10 -/- mice exposed to NMS, indicating mast cell activation. Conclusions: This study demonstrates that colitis in IL-10-/- mice can be exacerbated by NMS stress. The precise mechanisms of enhanced colitis severity in NMS IL10-/- mice are unclear but persistent defects in intestinal barrier function likely play a contributing role. NMS serves as a novel model to investigate the mechanisms by which early life stress influences the development and course of inflammatory bowel disease in adulthood.

Original languageEnglish
Pages (from-to)712-719
Number of pages8
JournalInflammatory Bowel Diseases
Volume19
Issue number4
DOIs
StatePublished - Mar 2013

Funding

FundersFunder number
National Institute of Diabetes and Digestive and Kidney DiseasesR01DK054452

    Keywords

    • Animal models of ibd
    • Barrier function
    • Colitis
    • Inflammatory bowel disease
    • Neonatal maternal separation
    • Psychological stress

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