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Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation
  1. Mélanie G Gareau1,
  2. Jennifer Jury1,
  3. Glenda MacQueen2,
  4. Philip M Sherman3,
  5. Mary H Perdue1
  1. 1
    Intestinal Disease Research Program, Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
  2. 2
    Department of Psychiatry, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
  3. 3
    Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  1. Mélanie G Gareau, 555 University Ave, Division of Gastroenterology, The Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8; melanie.gareau{at}


Background: We previously showed that neonatal maternal separation (MS) of rat pups causes immediate and long-term changes in intestinal physiology.

Aim: To examine if administration of probiotics affects MS-induced gut dysfunction.

Methods: MS pups were separated from the dam for 3 h/day from days 4 to 19; non-separated (NS) pups served as controls. Twice per day during the separation period, 108 probiotic organisms (two strains of Lactobacillus species) were administered to MS and NS pups; vehicle-treated pups received saline. Studies were conducted on day 20, when blood was collected for corticosterone measurement as an indication of hypothalamus–pituitary–adrenal (HPA) axis activity, and colonic function was studied in tissues mounted in Ussing chambers. Ion transport was indicated by baseline and stimulated short-circuit current (Isc); macromolecular permeability was measured by flux of horseradish peroxidase (HRP) across colonic tissues; and bacterial adherence/penetration into the mucosa was quantified by culturing tissues in selective media. Colonic function and host defence were also evaluated at day 60.

Results: Isc and HRP flux were significantly higher in the colon of MS versus NS pups. There was increased adhesion/penetration of total bacteria in MS pups, but a significant reduction in Lactobacillus species. Probiotic administration ameliorated the MS-induced gut functional abnormalities and bacterial adhesion/penetration at both day 20 and 60, and reduced the elevated corticosterone levels at day 20.

Conclusions: The results indicate that altered enteric flora are responsible for colonic pathophysiology. Probiotics improve gut dysfunction induced by MS, at least in part by normalisation of HPA axis activity.

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  • Funding: This research was supported by grants from the Canadian Institutes for Health Research and the Crohn’s and Colitis Foundation of Canada.

  • Competing interests: None.

  • Abbreviations:
    adrenocorticotrophic hormone
    colony-forming units
    corticotrophin-releasing hormone
    electrical field stimulation
    HPA axis
    hypothalamus–pituitary–adrenal axis
    horseradish peroxidase
    inflammatory bowel disease
    irritable bowel syndrome
    short-circuit current
    maternal separation
    secretory immunoglobulin A
    water avoidance stress

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  • Corrections
    BMJ Publishing Group Ltd and British Society of Gastroenterology