A murine model of pediatric inflammatory bowel disease causes microbiota-gut-brain axis deficits in adulthood

Eloisa Salvo, Patricia Stokes, Ciara E. Keogh, Ingrid Brust-Mascher, Carly Hennessey, Trina A. Knotts, Jessica A. Sladek, Kavi M. Rude, Michelle Swedek, Gonzalo Rabasa, Mélanie G. Gareau

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Inflammatory bowel diseases (IBDs) are chronic intestinal diseases, frequently associated with comorbid psychological and cognitive deficits. These neuropsychiatric effects include anxiety, depression, and memory impairments that can be seen both during active disease and following remission and are more frequently seen in pediatric patients. The mechanism(s) through which these extraintestinal deficits develop remain unknown, and the study of these phenomenon is hampered by a lack of murine pediatric IBD models. Herein we describe microbiota-gut-brain (MGB) axis deficits following induction of colitis in a pediatric setting. Acute colitis was induced by administration of 2% dextran sodium sulfate (DSS) for 5 days starting at weaning [postnatal day (P)21] causing reduced weight gain, colonic shortening, and colonic inflammation by 8 days post-DSS (P29), which were mostly resolved in adult (P56) mice. Despite resolution of acute disease, cognitive deficits (novel object recognition task) and anxiety-like behavior (light/dark box) were identified in the absence of changes in exploratory behavior (open field test) in P56 mice previously treated with DSS at weaning. Behavioral deficits were found in conjunction with neuroinflammation, decreased neurogenesis, and altered expression of pattern recognition receptor genes in the hippocampus. Additionally, persistent alterations in the gut microbiota composition were observed at P56, including reduced butyrate-producing species. Taken together, these results describe for the first time the presence of MGB axis deficits following induction of colitis at weaning, which persist in adulthood.

Original languageEnglish (US)
Pages (from-to)G361-G374
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume319
Issue number3
DOIs
StatePublished - Sep 2020

Keywords

  • Colitis
  • Gut-brain
  • Microbiota
  • Neurogenesis
  • Neuroinflammation

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'A murine model of pediatric inflammatory bowel disease causes microbiota-gut-brain axis deficits in adulthood'. Together they form a unique fingerprint.

Cite this