title: Protein kinase C δ signaling is required for dietary prebiotic-induced strengthening of intestinal epithelial barrier function.
abstract: Prebiotics are non-digestible oligosaccharides that promote the growth of beneficial gut microbes, but it is unclear whether they also have direct effects on the intestinal mucosal barrier. Here we demonstrate two commercial prebiotics, inulin and short-chain fructo-oligosaccharide (scFOS), when applied onto intestinal epithelia in the absence of microbes, directly promote barrier integrity to prevent pathogen-induced barrier disruptions. We further show that these effects involve the induction of select tight junction (TJ) proteins through a protein kinase C (PKC) δ-dependent mechanism. These results suggest that in the absence of microbiota, prebiotics can directly exert barrier protective effects by activating host cell signaling in the intestinal epithelium, which represents a novel alternative mechanism of action of prebiotics.
authors.affiliation: Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Richard Y
authors.initials: RY
authors.lastname: Wu
authors.affiliation: Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Majd
authors.initials: M
authors.lastname: Abdullah
authors.affiliation: Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Pekka
authors.initials: P
authors.lastname: Määttänen
authors.affiliation: Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Ana Victoria C
authors.initials: AV
authors.lastname: Pilar
authors.affiliation: Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Erin
authors.initials: E
authors.lastname: Scruten
authors.affiliation: Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Kathene C
authors.initials: KC
authors.lastname: Johnson-Henry
authors.affiliation: Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.|Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Napper
authors.affiliation: Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Canada.|University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: O'Brien
authors.affiliation: Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada.|Departments of Paediatrics and Physiology, University Toronto, Toronto, Ontario, Canada.
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Jones
authors.affiliation: Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Canada.|Department of Nutritional Sciences, University of Toronto, Toronto, Canada.|Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Sherman
mesh_terms: D018938:Caco-2 Cells; D002478:Cells, Cultured; D019587:Dietary Supplements; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D007444:Inulin / Q000494:pharmacology; D064307:Microbiota; D009844:Oligosaccharides / Q000494:pharmacology; D056692:Prebiotics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D009844:Oligosaccharides; D056692:Prebiotics; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D062725:Tight Junction Proteins; D051193:Toll-Like Receptors; D062826:Zonula Occludens-1 Protein; D007444:Inulin; D051745:Protein Kinase C-delta