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098 PROBIOTIC TREATMENT OF NEONATAL RATS NORMALIZES HPA-AXIS ACTIVITY AND PRODUCES LONG-LASTING BENEFICIAL EFFECTS ON GUT PATHOPHYSIOLOGY INDUCED BY MATERNAL SEPARATION MG Gareau1, J Jury1, G MacQueen2, PM Sherman3, MH Perdue1 BACKGROUND: We previously showed that neonatal maternal separation (MS) of rat pups causes immediate and long-term changes in intestinal physiology.
1Intestinal Disease Research Program, Department of Pathology and Molecular Medicine; 2Department of Psychiatry; 3Faculty of Health Sciences, McMaster University, Hamilton; Department of Pediatrics and Laboratory Medicine and Pathobiology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario
AIM: To examine if administration of probiotics affects MS-induced gut dysfunction.
METHODS: MS pups were separated from the dam for 3h/day from days 4-19; non-separated (NS) pups served as controls. Twice per day during the separation period, 109 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 hypothalamic-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; bacterial adherence/penetration into the mucosa was quantified by culturing tissues in selective media. Colonic function and host defense were also evaluated at day 60.
RESULTS: Isc and HRP flux were significantly higher in the colon of MS vs 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 both at day 20 and 60, and reduced the elevated corticosterone levels at day 20.
CONCLUSIONS: Our results indicate that altered enteric flora are responsible for colonic pathophysiology. Probiotics restore the balance of bacterial flora and improve gut dysfunction induced by MS, at least in part by normalization of HPA-axis activity.