Assessing the clinical value of faecal bile acid profiling to predict recurrence in primary Clostridioides difficile infection

Abstract

Summary 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 to 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.

Editorial: the acid test—can bile acids predict recurrence of Clostridioides difficile infection? Authors' reply

“…The authors' declarations of personal and financial interests are unchanged from those in the original article 2 …”

“…To view these articles, visit https://doi.org/10.1111/apt.17247 and https://doi. org/10.1111/apt.17266 Benjamin H. Mullish 1,2 Laura Martinez-Gili 1,3 Jessica R. Allegretti…”

“…6 Bacteroides are a major source of BSH within the gut microbiome, 7 and we noted that recovery of gut BSH functionality over time was only present among patients with nonrelapsing primary CDI. 2 Collectively, our observation of isodeoxycholic acid being strongly protective against primary CDI recurrence may reflect the balance between its actions in inhibiting growth of C. difficile, pitted against its ability to still allow recovery of commensal bacteria with BSH functionality within the microbiome post-CDI.…”

“…We thank Drs. Lo and Segal 1 for their editorial in response to our study, which explored faecal bile acid (BA) dynamics and sought BAs that may potentially predict recurrence in patients with primary Clostridioides difficile infection (CDI) 2 …”

Editorial: the acid test – can bile acids predict recurrence of Clostridioides difficile infection?

“…In those who responded to FMT, BSH activity recovered, which correlated with a reduction in taurocholate concentrations. Mullish and colleagues have provided further mechanistic insights into the clinical significance of specific faecal bile acid profiles 6 …”