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Human Clostridium difficile infection: altered mucus production and composition

Melinda A Engevik1, Mary Beth Yacyshyn2, Kristen A Engevik1

  • 1Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio;

American Journal of Physiology. Gastrointestinal and Liver Physiology
|January 2, 2015
PubMed

Insights

Clostridium difficile infection (CDI) alters intestinal mucus, decreasing MUC2 and changing oligosaccharides. This mucus composition facilitates C. difficile binding and colonization, suggesting new therapeutic targets.

Area of Science:

  • Gastroenterology
  • Microbiology
  • Immunology

Background:

  • Antibiotic-induced diarrhea is primarily caused by Clostridium difficile (C. difficile).
  • C. difficile infection (CDI) hospitalizations have significantly increased, necessitating a deeper understanding of its colonization mechanisms.
  • Intestinal mucus plays a crucial role in host-bacterial interactions and gut health.

Purpose of the Study:

  • To investigate changes in mucus production and composition in patients with CDI compared to healthy individuals.
  • To elucidate the role of mucus alterations in C. difficile colonization and infection.

Main Methods:

  • Analysis of MUC1 and MUC2 mucin expression and mucus oligosaccharide composition in healthy and CDI patients.
  • In vitro experiments assessing C. difficile growth on various sugars.
  • Human intestinal organoid (HIO) models to study C. difficile interaction with host mucus.
  • Binding assays comparing C. difficile adherence to mucus from healthy and CDI subjects.

Main Results:

  • CDI patients showed reduced MUC2 levels and altered mucus oligosaccharide profiles (decreased GalNAc, increased GlcNAc, and increased terminal galactose).
  • C. difficile can metabolize key mucus sugars for growth.
  • C. difficile alone reduced MUC2 production in HIOs but did not alter oligosaccharide composition.
  • C. difficile exhibited preferential binding to mucus from CDI patients.

Conclusions:

  • Altered intestinal mucus composition in CDI patients, particularly changes in MUC2 and specific oligosaccharides, may promote C. difficile colonization.
  • The increased presence of terminal galactose residues in CDI mucus is significant, as it acts as a receptor for C. difficile toxin A.
  • These findings offer insights into C. difficile pathogenesis and suggest potential targets for novel therapeutic interventions.
Keywords:
C. difficileMUC1MUC2intestinal organoidmucus oligosaccharides

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