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Human Colonoid Monolayers to Study Interactions Between Pathogens, Commensals, and Host Intestinal Epithelium
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A tertiary amino-containing polymethacrylate polymer protects mucus-covered intestinal epithelial monolayers against

Simon Keely1, Lee-Anne B Rawlinson, David M Haddleton

  • 1School of Agriculture, Food Science and Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.

Pharmaceutical Research
|November 30, 2007
PubMed
Abstract

Insights

The mucoadhesive polymer poly(DMAEMA) protects intestinal cells from toxins and bacteria, especially when mucus is present. It also directly kills S. typhimurium, showing potential as an anti-infective therapy.

Area of Science:

  • Gastroenterology
  • Polymer Science
  • Microbiology

Background:

  • Intestinal epithelial cells are vulnerable to bacterial toxins and pathogens.
  • Mucoadhesive polymers offer potential therapeutic strategies for gastrointestinal infections.

Purpose of the Study:

  • To investigate the cytoprotective effects of poly(DMAEMA) on human intestinal cells against bacterial toxins and S. typhimurium.
  • To assess the direct antibacterial activity of poly(DMAEMA) against S. typhimurium.

Main Methods:

  • Human intestinal epithelial monolayers were exposed to poly(DMAEMA) and challenged with cholera toxin, C. difficile toxin, or S. typhimurium.
  • Assays included LDH release, cytokine secretion, cAMP levels, and microscopy.
  • Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-kill studies were performed for poly(DMAEMA) against S. typhimurium.

Main Results:

  • Poly(DMAEMA) reduced toxin-induced LDH release and cAMP elevation.
  • In the presence of mucus, poly(DMAEMA) decreased S. typhimurium adherence and IL-8 secretion.
  • Poly(DMAEMA) demonstrated direct bactericidal activity against S. typhimurium at 1 mg/ml within 30 minutes.

Conclusions:

  • Poly(DMAEMA) exhibits cytoprotective effects against bacterial toxins and pathogens in the intestine.
  • The protective mechanism involves physical interaction with mucus and direct bacterial killing.
  • Poly(DMAEMA) shows promise as a non-absorbed polymer therapeutic for infections.

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