A short-term maternal separation in early neonate rats markedly increases intestinal permeability, induces bacterial translocation to systemic organs and impacts gene expression in the liver

ABSTRACT: Intestinal paracellular permeability (IPP) is high at birth and is involved in gut barrier maturation and liver development. Chronic maternal separation (MS) in early life alters intestinal barrier function in adulthood. However, only transient MS commonly occurs in human newborns, but whether a single episode of MS in early postnatal days (PND) affects the maturation of the gut-liver axis has not been explored. The aim of the current study was to evaluate the effect of a single MS of short duration in neonate rats on epithelial barrier integrity in the gut and on gene expression in the liver. Male and female pups were separated from their dams for 4h or not (controls) at PND10 or PND20. Total intestinal paracellular permeability (IPP) was measured through mucosal-to-plasma passage of oral FITC-Dextran 4 KD with or without ML7, a blocker of myosin light chain kinase (MLCK), or Mifepristone (RU486), an antagonist of the glucocorticoid receptor. Dose response to dexamethasone (DEX) on IPP was studied at PND10 and PND20. Bacterial translocation (BT) was assessed in mesenteric lymph nodes (MLN), liver and spleen in the presence or absence of ML7. The hepatic transcriptome was studied using Agilent microarrays and qPCR on PND10 rats pretreated or not with ML7. At PND10, control pups showed basal BT to MLN while liver and spleen were sterile. A short-term MS procedure increased IPP and plasma corticosterone levels, resulted in BT to the liver and spleen and had a clear impact on the hepatic transcriptome. Most notably, several genes involved in cell division were downregulated by MS. In PND10 rats, MS-induced increase of IPP and BT were blocked by ML7 or RU486, thus demonstrating a role of the MLCK pathway and of increased plasma levels of corticosterone in these effects of MS. All these effects of MS were absent in PND20 rats. Consistently, PND20 rats were found less sensitive to DEX exposure than PND10 rats. These results show that the early life period is a critical window for a short-term mother-infant separation, which can alter the development of the gut-liver axis and facilitate bacterial passage to systemic organs.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE44241 | GEO | 2016/02/01

SECONDARY ACCESSION(S): PRJNA189231

REPOSITORIES: GEO