Effets protecteurs d’un nouveau peptide bioactif issus des laits fermentés dans deux modèles de pathologies intestinales

Effets protecteurs d’un nouveau peptide bioactif issus des laits fermentés dans deux modèles de pathologies intestinales. 32. Réunion annuelle du Club d'Etudes des Cellules Epithéliales Digestives (CECED

Protective effects of beta-CN(94-123), a bioactive peptide present in fermented milk, in inflammation and stress-related gastrointestinal disorders

Protective effects of beta-CN(94-123), a bioactive peptide present in fermented milk, in inflammation and stress-related gastrointestinal disorders. Digestive Disease Wee

Oral administration of a casein matrix containing beta-casofensin protects the intestinal barrier in two preclinical models of gut diseases

β-Casofensin is a milk-derived bioactive peptide that interacts with intestinal goblet cells. We aimed to determine whether β-casofensin could prevent intestinal dysfunctions induced by neonatal maternal separation (NMS) and whether it retains its protective effects when administered in a casein matrix. We also evaluated whether a casein matrix enriched in β-casofensin protects against intestinal enteritis induced by indomethacin. β-Casofensin abolished NMS-induced jejunal hyperpermeability and prevented the depletion of goblet and Paneth cells induced by NMS. In addition, β-casofensin maintained its effectiveness against NMS-induced intestinal barrier alterations when administered in a casein matrix. A casein matrix containing β-casofensin also reduced intestinal damages induced by indomethacin. A functional food containing β-casofensin may prevent both the deleterious effects ofneonatal stress on the intestinal barrier and indomethacin-induced enteritis. These results suggest a promising application of β-casofensin as a gut barrier protector in the context of bioactive foods and clinical nutrition

Changes in intestinal glucocorticoid sensitivity in early life shape the risk of epithelial barrier defect in maternal-deprived rats.

Glucocorticoids (GC) contribute to human intestine ontogeny and accelerate gut barrier development in preparation to birth. Rat gut is immature at birth, and high intestinal GC sensitivity during the first two weeks of life resembles that of premature infants. This makes suckling rats a model to investigate postpartum impact of maternal separation (MS)-associated GC release in preterm babies, and whether GC sensitivity may shape MS effects in immature gut. A 4 hours-MS applied once at postnatal day (PND)10 enhanced plasma corticosterone in male and female pups, increased by two times the total in vivo intestinal permeability (IP) to oral FITC-Dextran 4 kDa (FD4) immediately after the end of MS, and induced bacterial translocation (BT) to liver and spleen. Ussing chamber experiments demonstrated a 2-fold increase of permeability to FD4 in the colon immediately after the end of MS, but not in the ileum. Colonic permeability was not only increased for FD4 but also to intact horseradish peroxidase 44 kDa in MS pups. In vivo, the glucocorticoid receptor (GR) antagonist RU486 or ML7 blockade of myosin light chain kinase controlling epithelial cytoskeleton contraction prevented MS-induced IP increase to oral FD4 and BT. In addition, the GR agonist dexamethasone dose-dependently mimicked MS-increase of IP to oral FD4. In contrast, MS effects on IP to oral FD4 and BT were absent at PND20, a model for full-term infant, characterized by a marked drop of IP to FD4 in response to dexamethasone, and decreased GR expression in the colon only compared to PND10 pups. These results show that high intestinal GC responsiveness in a rat model of prematurity defines a vulnerable window for a post-delivery MS, evoking immediate disruption of epithelial integrity in the large intestine, and increasing susceptibility to macromolecule passage and bacteremia

Perinatal exposure to a low dose of bisphenol A impaired systemic cellular immune response and predisposes young rats to intestinal parasitic infection.

Perinatal exposure to the food contaminant bisphenol A (BPA) in rats induces long lasting adverse effects on intestinal immune homeostasis. This study was aimed at examining the immune response to dietary antigens and the clearance of parasites in young rats at the end of perinatal exposure to a low dose of BPA. Female rats were fed with BPA [5 µg/kg of body weight/day] or vehicle from gestational day 15 to pup weaning. Juvenile female offspring (day (D)25) were used to analyze immune cell populations, humoral and cellular responses after oral tolerance or immunization protocol to ovalbumin (OVA), and susceptibility to infection by the intestinal nematode Nippostrongylus brasiliensis (N. brasiliensis). Anti-OVA IgG titers following either oral tolerance or immunization were not affected after BPA perinatal exposure, while a sharp decrease in OVA-induced IFNγ secretion occurred in spleen and mesenteric lymph nodes (MLN) of OVA-immunized rats. These results are consistent with a decreased number of helper T cells, regulatory T cells and dendritic cells in spleen and MLN of BPA-exposed rats. The lack of cellular response to antigens questioned the ability of BPA-exposed rats to clear intestinal infections. A 1.5-fold increase in N. brasiliensis living larvae was observed in the intestine of BPA-exposed rats compared to controls due to an inappropriate Th1/Th2 cytokine production in infected jejunal tissues. These results show that perinatal BPA exposure impairs cellular response to food antigens, and increases susceptibility to intestinal parasitic infection in the juveniles. This emphasized the maturing immune system during perinatal period highly sensitive to low dose exposure to BPA, altering innate and adaptative immune response capacities in early life