P-1558. Protective Bile Acid Profiles in Immunocompromised Pediatric Patients with Confirmed CDI Toxin

TL;DR

This study explores how bile acid profiles differ in children with C. diff toxin exposure but no symptoms, suggesting potential new diagnostic or therapeutic targets.

Contribution

The study identifies specific bile acids associated with symptom presence in toxin-positive C. diff cases, offering a novel metabolomic diagnostic approach.

Findings

Eight bile acids were significantly associated with symptomatic C. diff toxin positivity in pediatric patients.

Most CCNA-positive stool samples came from asymptomatic participants, indicating possible metabolic protection.

The findings suggest a potential role for bile acids in predicting CDI symptomology in immunocompromised children.

Abstract

Oncologic patients are disproportionately affected by Clostridioides difficile (C. diff) infection (CDI) due to increased risk factors, including those undergoing hematopoietic stem cell transplantation (HSCT). We have previously shown that pediatric patients have both colonization with toxigenic C. diff isolates and measurable toxin production without evidence of clinical disease. We aim to prove that establishing metabolomic protection despite toxin presence we can introduce a new potential target for therapeutics and help resolve the substantial diagnostic uncertainty.Summary of StatsBox Plot of Bile AcidsBile acids comparisons of symptomatic vs asymptomatic toxin positive patients

Summary of Stats

Box Plot of Bile Acids

Bile acids comparisons of symptomatic vs asymptomatic toxin positive patients

As part of a multi-center, prospective stool banking study, pediatric patients admitted with an oncologic diagnosis were enrolled between November 2019 to March 2023. A total of 98 participants were included and followed longitudinally for all subsequent inpatient admissions. Stool from children with CDI risk factors and surveys were collected weekly, and isolated C. diff were cultured, and Cell Cytotoxicity Neutralization Assay (CCNA) was performed. Following CCNA testing, bile acids were extracted from CCNA(+) stool using an organic solvent in beadruptor tubes for analysis by liquid chromatography-mass spectrometry. P-values were calculated using Wilcoxon rank-sum test with a significance threshold set at α = 0.05.Baseline CharacteristicsVolcano Plot

Baseline Characteristics

Volcano Plot

Of the 98 enrolled participants, the median age was 7 years (IQR: [3.5, 13.6]), and 45% and 52% were Caucasian and male, respectively. A total of 37 CCNA positive stool samples were sent for untargeted metabolomic profiling of bile acids. Of these, 78% of participants were asymptomatic at the time of collection. Eight bile acids were significantly up- or downregulated in the symptomatic cohort.

These preliminary findings suggested 8 bile acids are significantly associated with CDI symptomology; future work should validate these trends in larger samples.

All Authors: No reported disclosures

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