J Neurogastroenterol Motil.  2017 Jan;23(1):135-143. 10.5056/jnm16105.

Chronic Early-life Stress in Rat Pups Alters Basal Corticosterone, Intestinal Permeability, and Fecal Microbiota at Weaning: Influence of Sex

• Moussaoui
• Jacobs JP
• Larauche M
• Biraud M
• Million M
• Mayer E
• Taché Y

• KMID: 2367465
• DOI: http://doi.org/10.5056/jnm16105

Abstract

BACKGROUND/AIMS
Wistar rat dams exposed to limited nesting stress (LNS) from post-natal days (PND) 2 to 10 display erratic maternal behavior, and their pups show delayed maturation of the hypothalamic-pituitary-adrenal axis and impaired epithelial barrier at PND10 and a visceral hypersensitivity at adulthood. Little is known about the impact of early life stress on the offspring before adulthood and the influence of sex. We investigated whether male and female rats previously exposed to LNS displays at weaning altered corticosterone, intestinal permeability, and microbiota.
METHODS
Wistar rat dams and litters were maintained from PND2 to 10 with limited nesting/bedding materials and thereafter reverted to normal housing up to weaning (PND21). Control litters had normal housing. At weaning, we monitored body weight, corticosterone plasma levels (enzyme immunoassay), in vivo intestinal to colon permeability (fluorescein isothiocyanate-dextran 4 kDa) and fecal microbiota (DNA extraction and amplification of the V4 region of the 16S ribosomal RNA gene).
RESULTS
At weaning, LNS pups had hypercorticosteronemia and enhanced intestinal permeability with females > males while body weights were similar. LNS decreased fecal microbial diversity and induced a distinct composition characterized by increased abundance of Gram positive cocci and reduction of fiber-degrading, butyrate-producing, and mucus-resident microbes.
CONCLUSIONS
These data indicate that chronic exposure to LNS during the first week post-natally has sustained effects monitored at weaning including hypercorticosteronemia, a leaky gut, and dysbiosis. These alterations may impact on the susceptibility to develop visceral hypersensitivity in adult rats and have relevance to the development of irritable bowel syndrome in childhood.

Keyword

Corticosterone; Microbiota; Permeability; Stress; psychological; Weaning

MeSH Terms

Adult
Animals
Body Weight
Colon
Corticosterone*
Dysbiosis
Female
Gram-Positive Cocci
Housing
Humans
Hypersensitivity
Irritable Bowel Syndrome
Male
Maternal Behavior
Microbiota*
Permeability*
Plasma
Rats*
RNA, Ribosomal, 16S
Stress, Psychological
Weaning*
Corticosterone
RNA, Ribosomal, 16S