Lactobacillus reuteri in its biofilm state promotes neurodevelopment after experimental necrotizing enterocolitis in rats

Necrotizing enterocolitis (NEC) is a devastating disease affecting premature newborns with no known cure. Up to half of survivors subsequently exhibit cognitive impairment and neurodevelopmental defects. We created a novel probiotics delivery system in which the probiotic Lactobacillus reuteri (Lr)...

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Main Authors: Yijie Wang, Robert M. Jaggers, Pamela Mar, Jeffrey D. Galley, Terri Shaffer, Adrian Rajab, Shivani Deshpande, Lauren Mashburn-Warren, John R. Buzzo, Steven D. Goodman, Michael T. Bailey, Gail E. Besner
Format: Article
Language:English
Published: Elsevier 2021-07-01
Series:Brain, Behavior, & Immunity - Health
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666354621000594
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language English
format Article
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author Yijie Wang
Robert M. Jaggers
Pamela Mar
Jeffrey D. Galley
Terri Shaffer
Adrian Rajab
Shivani Deshpande
Lauren Mashburn-Warren
John R. Buzzo
Steven D. Goodman
Michael T. Bailey
Gail E. Besner
spellingShingle Yijie Wang
Robert M. Jaggers
Pamela Mar
Jeffrey D. Galley
Terri Shaffer
Adrian Rajab
Shivani Deshpande
Lauren Mashburn-Warren
John R. Buzzo
Steven D. Goodman
Michael T. Bailey
Gail E. Besner
Lactobacillus reuteri in its biofilm state promotes neurodevelopment after experimental necrotizing enterocolitis in rats
Brain, Behavior, & Immunity - Health
Necrotizing enterocolitis (NEC)
Cognitive function
Learning
Memory
Probiotics
Lactobacillus reuteri
author_facet Yijie Wang
Robert M. Jaggers
Pamela Mar
Jeffrey D. Galley
Terri Shaffer
Adrian Rajab
Shivani Deshpande
Lauren Mashburn-Warren
John R. Buzzo
Steven D. Goodman
Michael T. Bailey
Gail E. Besner
author_sort Yijie Wang
title Lactobacillus reuteri in its biofilm state promotes neurodevelopment after experimental necrotizing enterocolitis in rats
title_short Lactobacillus reuteri in its biofilm state promotes neurodevelopment after experimental necrotizing enterocolitis in rats
title_full Lactobacillus reuteri in its biofilm state promotes neurodevelopment after experimental necrotizing enterocolitis in rats
title_fullStr Lactobacillus reuteri in its biofilm state promotes neurodevelopment after experimental necrotizing enterocolitis in rats
title_full_unstemmed Lactobacillus reuteri in its biofilm state promotes neurodevelopment after experimental necrotizing enterocolitis in rats
title_sort lactobacillus reuteri in its biofilm state promotes neurodevelopment after experimental necrotizing enterocolitis in rats
publisher Elsevier
series Brain, Behavior, & Immunity - Health
issn 2666-3546
publishDate 2021-07-01
description Necrotizing enterocolitis (NEC) is a devastating disease affecting premature newborns with no known cure. Up to half of survivors subsequently exhibit cognitive impairment and neurodevelopmental defects. We created a novel probiotics delivery system in which the probiotic Lactobacillus reuteri (Lr) was induced to form a biofilm [Lr (biofilm)] by incubation with dextranomer microspheres loaded with maltose (Lr-DM-maltose). We have previously demonstrated that a single dose of the probiotic Lr administered in its biofilm state significantly reduces the incidence of NEC and decreases inflammatory cytokine production in an animal model of the disease. The aim of our current study was to determine whether a single dose of the probiotic Lr administered in its biofilm state protects the brain after experimental NEC. We found that rat pups exposed to NEC reached developmental milestones significantly slower than breast fed pups, with mild improvement with Lr (biofilm) treatment. Exposure to NEC had a negative effect on cognitive behavior, which was prevented by Lr (biofilm) treatment. Lr administration also reduced anxiety-like behavior in NEC-exposed rats. The behavioral effects of NEC were associated with increased numbers of activated microglia, decreased myelin basic protein (MBP), and decreased neurotrophic gene expression, which were prevented by administration of Lr (biofilm). Our data indicate early enteral treatment with Lr in its biofilm state prevented the deleterious effects of NEC on developmental impairments.
topic Necrotizing enterocolitis (NEC)
Cognitive function
Learning
Memory
Probiotics
Lactobacillus reuteri
url http://www.sciencedirect.com/science/article/pii/S2666354621000594
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spelling doaj-b71d192ed7914402930ad7d002ccbb882021-06-10T04:58:17ZengElsevierBrain, Behavior, & Immunity - Health2666-35462021-07-0114100256Lactobacillus reuteri in its biofilm state promotes neurodevelopment after experimental necrotizing enterocolitis in ratsYijie Wang0Robert M. Jaggers1Pamela Mar2Jeffrey D. Galley3Terri Shaffer4Adrian Rajab5Shivani Deshpande6Lauren Mashburn-Warren7John R. Buzzo8Steven D. Goodman9Michael T. Bailey10Gail E. Besner11Center for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Department of Pediatric Surgery, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USACenter for Microbial Pathogenesis, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USACenter for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Department of Pediatric Surgery, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USACenter for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Department of Pediatric Surgery, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USAPreclinical Imaging and Behavior Core/Animal Resources Core, The Research Institute at Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USACenter for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Department of Pediatric Surgery, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USACenter for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Department of Pediatric Surgery, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USACenter for Microbial Pathogenesis, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USACenter for Microbial Pathogenesis, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USACenter for Microbial Pathogenesis, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USACenter for Microbial Pathogenesis, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USACenter for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Department of Pediatric Surgery, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USA; Corresponding author. Department of Pediatric Surgery, FB6135, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USA.Necrotizing enterocolitis (NEC) is a devastating disease affecting premature newborns with no known cure. Up to half of survivors subsequently exhibit cognitive impairment and neurodevelopmental defects. We created a novel probiotics delivery system in which the probiotic Lactobacillus reuteri (Lr) was induced to form a biofilm [Lr (biofilm)] by incubation with dextranomer microspheres loaded with maltose (Lr-DM-maltose). We have previously demonstrated that a single dose of the probiotic Lr administered in its biofilm state significantly reduces the incidence of NEC and decreases inflammatory cytokine production in an animal model of the disease. The aim of our current study was to determine whether a single dose of the probiotic Lr administered in its biofilm state protects the brain after experimental NEC. We found that rat pups exposed to NEC reached developmental milestones significantly slower than breast fed pups, with mild improvement with Lr (biofilm) treatment. Exposure to NEC had a negative effect on cognitive behavior, which was prevented by Lr (biofilm) treatment. Lr administration also reduced anxiety-like behavior in NEC-exposed rats. The behavioral effects of NEC were associated with increased numbers of activated microglia, decreased myelin basic protein (MBP), and decreased neurotrophic gene expression, which were prevented by administration of Lr (biofilm). Our data indicate early enteral treatment with Lr in its biofilm state prevented the deleterious effects of NEC on developmental impairments.http://www.sciencedirect.com/science/article/pii/S2666354621000594Necrotizing enterocolitis (NEC)Cognitive functionLearningMemoryProbioticsLactobacillus reuteri