Microbiome and Bile Acid Profiles in Initial vs Recurrent Clostridioides difficile Infection

Overview

This analysis compared gastrointestinal microbiome diversity and bile acid composition in patients with first (frCDI) and multiply recurrent Clostridioides difficile infections (mrCDI) treated with the live microbiome therapeutic VOWST® (VOS). Both groups exhibited similarly low baseline microbial diversity and elevated primary bile acids, which improved after VOS treatment, resulting in low recurrence rates in both subgroups.

Background

Clostridioides difficile infection (CDI) often recurs after antibiotic treatment, with recurrence rates of 20–25% after a first episode and over 40% after multiple recurrences. Disruption of the gastrointestinal microbiome, characterized by reduced microbial diversity and altered bile acid metabolism, promotes C. difficile spore germination and toxin production. Current antibiotic therapies do not restore microbiome balance and may perpetuate recurrence. VOWST® (VOS), an FDA-approved oral microbiome therapeutic composed of Firmicutes spores, has demonstrated efficacy in reducing CDI recurrence by restoring microbial diversity and bile acid balance.

Data Highlights

Key Findings

• Baseline microbial diversity was similarly low in both first and multiply recurrent CDI patients.
• Primary bile acid concentrations were elevated and secondary bile acids depleted at baseline in both groups.
• Following VOS treatment, microbial diversity and secondary bile acid levels increased, while primary bile acids decreased in both frCDI and mrCDI patients.
• CDI recurrence rates through 8 weeks post-treatment were low and comparable between frCDI (6.5%) and mrCDI (9.7%) groups.
• These findings suggest common microbiome disruptions contribute to recurrence regardless of prior CDI episodes.

Clinical Implications

The similar microbiome and bile acid profiles in first and multiply recurrent CDI patients support the use of microbiome restoration therapies like VOS early in the treatment course. Antibiotics followed by live microbiome therapeutics may optimize prevention of recurrence by rebalancing bile acid metabolism and restoring microbial diversity. This approach could be considered even after initial CDI episodes in patients at high risk for recurrence.

Conclusion

Microbiome disruption and bile acid imbalance are common to both initial and recurrent CDI, and treatment with VOS effectively restores these parameters, resulting in low recurrence rates. These data support microbiome therapeutic use across CDI episodes to improve sustained clinical outcomes.

References

1. Feuerstadt et al. 2023 -- ECOSPOR IV Trial of VOWST in CDI
2. American Gastroenterological Association 2023 -- Clinical Practice Guidelines for CDI
3. Khanna et al. 2016 -- Microbiome and CDI Recurrence