A Metabolomic Investigation Into Clostridium Difficile Infection

Open Access
Thal, Karissa Allan
Area of Honors:
Bachelor of Science
Document Type:
Thesis Supervisors:
  • Andrew Patterson, Thesis Supervisor
  • Stephen Wade Schaeffer, Honors Advisor
  • Metabolomics
  • Clostridium Difficile
Clostridium difficile (C.difficile) is the leading cause of healthcare-associated diarrhea in North America and Europe. The infection has been increasing steadily in incidence, severity, and mortality for the past decade due to the development of the epidemic strain BI/NAP1/027. Currently, a biomarker for C.difficile infection (CDI) does not exist, but could significantly improve early diagnosis of the infection, thus reducing morbidity and mortality. This study featured a comparative analysis of the urinary metabolic profiles of control subjects to those with CDI. It was hypothesized that differences in the urinary CDI metabolite profile, urinary endogenous metabolite profile, or both, would be detectable by metabolomics, and these differences will be of great potential value in identifying a biomarker of CDI. Comparison of the ultra high pressure liquid chromatography coupled with electrospray ionization quadruple time-of-flight mass spectrometry results between the Surgical Control and CDI groups revealed two endogenous compounds, p-cresol sulfate and indoxylsulfate, to be significantly elevated in the CDI group. However, this result was not consistent in the comparison between the Control and CDI groups. P-cresol sulfate and indoxylsulfate were therefore not conclusively implicated to be biomarkers of CDI. The results of 1H nuclear magnetic resonance spectroscopy revealed several endogenous compounds that were either significantly elevated or depressed in the CDI group relative to the Controls. However, due to the heavy antibiotic dosage that the CDI group was exposed to and the altered gut microbiota, we could not conclusively attribute a differential metabolite to be an endogenous biomarker of CDI.