title: L. fermentum CECT 5716 prevents stress-induced intestinal barrier dysfunction in newborn rats.
abstract: BACKGROUND
  Intestinal epithelial barrier (IEB) dysfunction plays a critical role in various intestinal disorders affecting infants and children, including the development of food allergies and colitis. Recent studies highlighted the role of probiotics in regulating IEB functions and behavior in adults, but their effects in the newborn remain largely unknown. We therefore characterized in rat pups, the impact of Lactobacillus fermentum CECT 5716 (L. fermentum) on stress-induced IEB dysfunction, systemic immune response and exploratory behavior.
  
  
  METHODS
  Newborn rats received daily by gavage either L. fermentum or water. Intestinal permeability to fluorescein sulfonic acid (FSA) and horseradish peroxidase (HRP) was measured following maternal separation (MS) and water avoidance stress (WAS). Immunohistochemical, transcriptomic, and Western blot analysis of zonula occludens-1 (ZO-1) distribution and expression were performed. Anxiety-like and exploratory behavior was assessed using the elevated plus maze test. Cytokine secretion of activated splenocytes was also evaluated.
  
  
  RESULTS
  L. fermentum prevented MS and WAS-induced IEB dysfunction in vivo. L. fermentum reduced permeability to both FSA and HRP in the small intestine but not in the colon. L. fermentum increased expression of ZO-1 and prevented WAS-induced ZO-1 disorganization in ileal epithelial cells. L. fermentum also significantly reduced stress-induced increase in plasma corticosteronemia. In activated splenocytes, L. fermentum enhanced IFNγ secretion while it prevented IL-4 secretion. Finally, L. fermentum increased exploratory behavior.
  
  
  CONCLUSIONS
  These results suggest that L. fermentum could provide a novel tool for the prevention and/or treatment of gastrointestinal disorders associated with altered IEB functions in the newborn.
authors.affiliation: INSERM U1235, Nantes, France.|Université de Nantes, Nantes, France.|Institut des Maladies de l'Appareil Digestif, Nantes, France.|Lactalis Recherche et Développement, Retiers, France.
authors.forename: T
authors.identifier: http://orcid.org/0000-0001-9980-1657
authors.initials: T
authors.lastname: Vanhaecke
authors.affiliation: INSERM U1235, Nantes, France.|Université de Nantes, Nantes, France.|Institut des Maladies de l'Appareil Digestif, Nantes, France.
authors.forename: P
authors.initials: P
authors.lastname: Aubert
authors.affiliation: INSERM U1235, Nantes, France.|Université de Nantes, Nantes, France.|Institut des Maladies de l'Appareil Digestif, Nantes, France.
authors.forename: P-A
authors.initials: PA
authors.lastname: Grohard
authors.affiliation: INSERM U1235, Nantes, France.|Université de Nantes, Nantes, France.|Institut des Maladies de l'Appareil Digestif, Nantes, France.
authors.forename: T
authors.initials: T
authors.lastname: Durand
authors.affiliation: Université de Nantes, Nantes, France.|MicroPICell - Cellular and Tissular Imaging Core Facility of Nantes, SFR Santé F. Bonamy-FED 4203/Inserm UMS016/CNRS UMS3556, Nantes, France.
authors.forename: P
authors.initials: P
authors.lastname: Hulin
authors.affiliation: Université de Nantes, Nantes, France.|MicroPICell - Cellular and Tissular Imaging Core Facility of Nantes, SFR Santé F. Bonamy-FED 4203/Inserm UMS016/CNRS UMS3556, Nantes, France.
authors.forename: P
authors.initials: P
authors.lastname: Paul-Gilloteaux
authors.affiliation: Normandie Univ, UNICAEN, INSERM, Physiopathology and Imaging of Neurological Disorders (PhIND), Centre Cyceron, Caen, France.
authors.forename: A
authors.initials: A
authors.lastname: Fournier
authors.affiliation: Normandie Univ, UNICAEN, INSERM, Physiopathology and Imaging of Neurological Disorders (PhIND), Centre Cyceron, Caen, France.
authors.forename: F
authors.initials: F
authors.lastname: Docagne
authors.affiliation: Lactalis Recherche et Développement, Retiers, France.
authors.forename: A
authors.initials: A
authors.lastname: Ligneul
authors.affiliation: Lactalis Nutrition Europe, Torcé, France.
authors.forename: C
authors.initials: C
authors.lastname: Fressange-Mazda
authors.affiliation: INSERM U1235, Nantes, France.|Université de Nantes, Nantes, France.|Institut des Maladies de l'Appareil Digestif, Nantes, France.
authors.forename: P
authors.initials: P
authors.lastname: Naveilhan
authors.affiliation: INSERM U1235, Nantes, France.|Université de Nantes, Nantes, France.|Institut des Maladies de l'Appareil Digestif, Nantes, France.
authors.forename: H
authors.initials: H
authors.lastname: Boudin
authors.affiliation: Lactalis Recherche et Développement, Retiers, France.
authors.forename: P
authors.initials: P
authors.lastname: Le Ruyet
authors.affiliation: INSERM U1235, Nantes, France.|Université de Nantes, Nantes, France.|Institut des Maladies de l'Appareil Digestif, Nantes, France.
authors.forename: M
authors.identifier: http://orcid.org/0000-0003-1892-5071
authors.initials: M
authors.lastname: Neunlist
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003106:Colon / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005106:Exploratory Behavior; D005260:Female; D005767:Gastrointestinal Diseases / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D007413:Intestinal Mucosa / Q000378:metabolism*; D052197:Limosilactobacillus fermentum; D008426:Maternal Deprivation; D010539:Permeability; D019936:Probiotics / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000150:complications*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein
keywords: Intestinal epithelial permeability; ZO-1; corticosterone; newborn; probiotic