Toxigenic Clostridium perfringens Isolated from At-Risk Paediatric Inflammatory Bowel Disease Patients

James Kuo1, Jasmina Uzunovic2, Amanda Jacobson3

  • 1Department of Infectious Diseases and Host-Microbe Interactions, Genentech Inc., South San Francisco, CA, USA.

PubMed
Abstract

Insights

Certain toxigenic Clostridium perfringens strains, particularly those producing perfringolysin O, may drive inflammatory bowel disease (IBD) progression and symptoms. Monitoring these bacteria and toxins is recommended for IBD patients.

Area of Science:

  • Microbiology
  • Gastroenterology
  • Immunology

Background:

  • Inflammatory bowel disease (IBD) pathogenesis involves complex interactions between host immunity and the gut microbiome.
  • Identifying specific microbial contributors to IBD is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate mucosal-associated bacteria and their toxic products as potential drivers of IBD.
  • To characterize the role of Clostridium perfringens in IBD patients.

Main Methods:

  • Direct culture of bacterial communities from pediatric gastrointestinal mucosal biopsies.
  • Assessment of pathogenicity-associated traits and toxin characterization.
  • Prevalence analysis in large IBD patient datasets and in vitro toxicity assays.

Main Results:

  • Clostridium perfringens was frequently detected in IBD mucosal biopsies, correlating with hemolytic activity.
  • C. perfringens toxins, specifically perfringolysin O (PFO), demonstrated in vitro toxicity to cells beneath the intestinal barrier.
  • C. perfringens supernatants induced neuroblast activation, suggesting a role in IBD-associated abdominal pain.

Conclusions:

  • Toxigenic C. perfringens strains in the gastrointestinal tract may significantly impact IBD pathogenesis.
  • Routine monitoring for C. perfringens and its toxins, like PFO, is warranted in IBD patients.
  • These findings suggest potential therapeutic strategies targeting C. perfringens in IBD management.