Protein kinase C δ signaling is required for dietary prebiotic-induced strengthening of intestinal epithelial barrier function

Sci Rep. 2017 Jan 18:7:40820. doi: 10.1038/srep40820.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Cells, Cultured
  • Dietary Supplements
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology
  • Inulin / pharmacology
  • Microbiota
  • Oligosaccharides / pharmacology
  • Prebiotics*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Kinase C-delta / antagonists & inhibitors
  • Protein Kinase C-delta / genetics
  • Protein Kinase C-delta / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction / drug effects
  • Tight Junction Proteins / genetics
  • Tight Junction Proteins / metabolism
  • Toll-Like Receptors / metabolism
  • Up-Regulation / drug effects
  • Zonula Occludens-1 Protein / genetics
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Oligosaccharides
  • Prebiotics
  • Protein Isoforms
  • RNA, Small Interfering
  • Tight Junction Proteins
  • Toll-Like Receptors
  • Zonula Occludens-1 Protein
  • Inulin
  • Protein Kinase C-delta