Assessing the clinical value of faecal bile acid profiling to predict recurrence in primary Clostridioides difficile infection
File(s)
Accepted version
Author(s)
Mullish, Benjamin H
Martinez Gili, Laura
Chekmeneva, Elena
Dos Santos Correia, Gonçalo DS
Lewis, Matthew R
Type
Journal Article
Abstract
Background:
Factors influencing recurrence risk in primary Clostridioides difficile infection (CDI) are poorly understood, and tools predicting recurrence are lacking. Perturbations in bile acids (BAs) contribute to CDI pathogenesis and may be relevant to primary disease prognosis.
Aims:
To define stool BA dynamics in patients with primary CDI and explore signatures predicting recurrence
Methods
Weekly stool samples were collected from patients with primary CDI from the last day of anti-CDI therapy until recurrence or, otherwise, through 8 weeks post-completion. Ultra-high performance liquid chromatography-mass spectrometry was used to profile BAs; stool bile salt hydrolase (BSH) activity was measured to determine primary BA bacterial deconjugation capacity. Multivariate and univariate models were used to define differential BA trajectories in patients with recurrence versus those without, and to assess faecal BAs as predictive markers for recurrence.
Results:
Twenty (36%) of 56 patients (median age: 57, 64% male) had recurrence; 80% of recurrences occurred within the first 9 days post-antibiotic treatment. Principal component analysis of stool BA profiles demonstrated clustering by recurrence status and post-treatment timepoint. Longitudinal faecal BA trajectories showed recovery of secondary BAs and their derivatives only in patients without recurrence. BSH activity increased over time only among non-relapsing patients (β = 0.056; likelihood ratio test p = 0.018). A joint longitudinal-survival model identified five stool BAs with area under the receiver operating characteristic curve >0.73 for predicting recurrence within 9 days post-CDI treatment.
Conclusions:
Gut BA metabolism dynamics differ in primary CDI patients between those developing recurrence and those who do not. Individual BAs show promise as potential novel biomarkers to predict CDI recurrence.
Factors influencing recurrence risk in primary Clostridioides difficile infection (CDI) are poorly understood, and tools predicting recurrence are lacking. Perturbations in bile acids (BAs) contribute to CDI pathogenesis and may be relevant to primary disease prognosis.
Aims:
To define stool BA dynamics in patients with primary CDI and explore signatures predicting recurrence
Methods
Weekly stool samples were collected from patients with primary CDI from the last day of anti-CDI therapy until recurrence or, otherwise, through 8 weeks post-completion. Ultra-high performance liquid chromatography-mass spectrometry was used to profile BAs; stool bile salt hydrolase (BSH) activity was measured to determine primary BA bacterial deconjugation capacity. Multivariate and univariate models were used to define differential BA trajectories in patients with recurrence versus those without, and to assess faecal BAs as predictive markers for recurrence.
Results:
Twenty (36%) of 56 patients (median age: 57, 64% male) had recurrence; 80% of recurrences occurred within the first 9 days post-antibiotic treatment. Principal component analysis of stool BA profiles demonstrated clustering by recurrence status and post-treatment timepoint. Longitudinal faecal BA trajectories showed recovery of secondary BAs and their derivatives only in patients without recurrence. BSH activity increased over time only among non-relapsing patients (β = 0.056; likelihood ratio test p = 0.018). A joint longitudinal-survival model identified five stool BAs with area under the receiver operating characteristic curve >0.73 for predicting recurrence within 9 days post-CDI treatment.
Conclusions:
Gut BA metabolism dynamics differ in primary CDI patients between those developing recurrence and those who do not. Individual BAs show promise as potential novel biomarkers to predict CDI recurrence.
Date Issued
2022-12
Date Acceptance
2022-09-27
Citation
Alimentary Pharmacology and Therapeutics, 2022, 56 (11-12), pp.1556-1569
ISSN
0269-2813
Publisher
Wiley
Start Page
1556
End Page
1569
Journal / Book Title
Alimentary Pharmacology and Therapeutics
Volume
56
Issue
11-12
Copyright Statement
© 2022 John Wiley & Sons Ltd. This is the peer reviewed version of the following article, which has been published in final form at https://onlinelibrary.wiley.com/doi/10.1111/apt.17247. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Sponsor
Medical Research Council
Medical Research Council (MRC)
Imperial College London Joint Translational Fund
Imperial College Healthcare NHS Trust- BRC Funding
Identifier
https://onlinelibrary.wiley.com/doi/10.1111/apt.17247
Grant Number
MR/R00875/1
MR/R000875/1
RDA02
Subjects
Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
Pharmacology & Pharmacy
GUT MICROBIOTA
HEALTH
CHROMATOGRAPHY
EPIDEMIOLOGY
ANTIBIOTICS
METABOLOME
VANCOMYCIN
GUIDELINES
DIAGNOSIS
MODULATE
Humans
Male
Middle Aged
Female
Clostridioides difficile
Bile Acids and Salts
Recurrence
Clostridium Infections
Feces
Feces
Humans
Clostridium Infections
Recurrence
Bile Acids and Salts
Middle Aged
Female
Male
Clostridioides difficile
Gastroenterology & Hepatology
1103 Clinical Sciences
1115 Pharmacology and Pharmaceutical Sciences
Publication Status
Published
Date Publish Online
2022-10-17