Abstract
Background
Despite advances in the understanding and diagnosis of
Clostridioides difficile Infection (CDI), clinical distinction within the colonization-infection continuum remains an unmet need.
Methods
By measuring stool cytokines and anti-toxin antibodies in well-characterized cohorts of
CDI (diarrhea, Nucleic Acid Amplification Test [NAAT]+), Non-CDI diarrhea (
NCD; diarrhea, NAAT-), asymptomatic carriers (
ASC; no diarrhea, NAAT+) and hospital controls (
CON, no diarrhea, NAAT-), we aim to discover novel biological markers to distinguish between these cohorts. We also explore the relationship of these stool cytokines and anti-toxin antibody with stool toxin concentrations and disease severity.
Results
Stool interleukin ( IL)-1β, stool IgA, and IgG anti-toxin A had higher (p < 0.0001) concentrations in CDI (n = 120) vs. ASC (n = 43), whereas toxins A, B, and fecal calprotectin did not. Areas Under the Receiver Operator Curve (ROC-AUCs) for IL-1β, IgA, and IgG anti-toxin A were 0.88, 0.83, and 0.83, respectively. A multi-predictor model including IL-1β and IgA anti-toxin A achieved a ROC-AUC of 0.93. Stool IL-1β concentrations were higher in CDI compared to NCD (n = 75), p < 0.0001, and NCD + ASC + CON (CON, n = 75), p < 0.0001, with ROC-AUCs of 0.83 and 0.86, respectively. Stool IL-1β had positive correlations with toxins A (ρ
A=+0.55) and B (ρ
B=+0.49) in CDI (p < 0.0001) but not in ASC (p > 0.05).
Conclusion
Stool concentrations of the inflammasome pathway, pro-inflammatory cytokine IL-1β can accurately differentiate CDI from asymptomatic carriage and non-CDI diarrhea, making it a promising biomarker for CDI diagnosis. Significant positive correlations exist between stool toxins and stool IL-1β in CDI but not in asymptomatic carriers.
