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Mélanie G Gareau1, Jennifer Jury, Glenda MacQueen
1Intestinal Disease Research Program, Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada. melanie.gareau@utoronto.ca
Insights
Neonatal maternal separation (MS) in rats causes gut dysfunction. Probiotic administration improved these gut issues and normalized stress hormone levels, suggesting altered gut bacteria contribute to the problem.
Area of Science:
- Gastroenterology
- Microbiology
- Neuroendocrinology
Background:
- Neonatal maternal separation (MS) in rat pups induces significant immediate and long-term alterations in intestinal physiology.
- Early life stress is known to impact gut health and the developing enteric nervous system.
Purpose of the Study:
- To investigate the therapeutic potential of probiotic administration in mitigating gut dysfunction caused by neonatal maternal separation.
- To assess the effect of probiotics on gut physiology, bacterial adherence, and hypothalamus-pituitary-adrenal (HPA) axis activity in a rat model of early life stress.
Main Methods:
- Rat pups underwent daily maternal separation (MS) or were non-separated (NS) controls from postnatal days 4-19.
- Probiotics (Lactobacillus species) or vehicle were administered twice daily during the separation period.
- Colonic function (ion transport, macromolecular permeability), bacterial adherence/penetration, and corticosterone levels were assessed on days 20 and 60.
Main Results:
- MS pups exhibited increased colonic ion transport (Isc) and macromolecular permeability (HRP flux) compared to NS controls.
- MS led to increased bacterial adhesion/penetration and a decrease in Lactobacillus species in the colon.
- Probiotic treatment ameliorated MS-induced gut dysfunction, reduced bacterial adhesion/penetration, and lowered elevated corticosterone levels.
Conclusions:
- Altered enteric microbiota composition is a key factor in the colonic pathophysiology observed after neonatal maternal separation.
- Probiotics demonstrate efficacy in improving gut dysfunction induced by MS, partly through the normalization of HPA axis activity.
- These findings highlight the gut microbiome-brain axis as a therapeutic target for stress-induced gastrointestinal disorders.
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, 10(8) 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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