Re-establishing bile acid composition after treatment of recurrent Clostridioides difficile infection with fecal microbiota transplantation compared with oral vancomycin or a 12-strain bacterial mixture

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: All treatment groups achieved donor-like bile acid composition

• Primary Outcome: Restoration of bile acid composition to donor-like secondary bile acid dominance

• Nnt Or Sensitivity: Approximately 50% of participants showed timely association between secondary bile acid rise and bile acid-transforming bacteria detection

• Confidence Interval: Not reported

Clinical Application

FMT requires specialised centres and donor screening; vancomycin is widely available; bacterial mixtures may offer standardised alternative FMT is available through TGA Special Access Scheme; vancomycin is PBS-listed for C. difficile; findings support RACGP guidelines on recurrent CDI management Patients with recurrent C. difficile infection suitable for FMT, vancomycin therapy, or bacterial mixture treatment

Abstract

Patients with Clostridioides difficile infection have high colonic levels of primary bile acids, which are potent germinators of Clostridioides difficile. Several studies have suggested that re-establishing a normal bile acid composition is a key factor in fecal microbiota transplantation (FMT) for recurrent C. difficile infection, yet former studies supporting this lacked controls. In a subgroup from a randomized controlled trial, we compared the bile acid composition in patients with recurrent C. difficile infection treated with either FMT, a bacterial mixture, or vancomycin. The fecal bile acid content was analyzed several times before and after treatments. Furthermore, we used 16S rDNA gene sequencing to analyze the presence of some bacterial species involved in bile acid metabolism. Stool donors served as healthy controls. We observed a higher proportion of primary bile acids in patients with recurrent C. difficile infection than in donors, yet a donor-like dominance of secondary bile acids was observed after successful treatment in all groups. The shift seemed to occur earliest in the FMT group, followed by the vancomycin group, and the latest in the bacterial mixture group. In approximately half of the participants, the rise in secondary bile acids was timely associated with the detection of bile acid-transforming bacteria that were absent before treatment. Our findings indicate that FMT re-establishes the bile acid composition faster than vancomycin, reducing the time of susceptibility to recurrences of C. difficile infection. Hence, bacterial mixtures developed as an alternative to donor stool for treating recurrent C. difficile infection might benefit from including bile acid-metabolizing bacteria.

References

1. 1.Rode, A. A., Duboc, H., Lamazière, A., Rainteau, D., Humbert, L., Gauliard, E., Chehri, M., Petersen, A. M., Helms, M., Schønning, K., Nielsen, H. V., Bytzer, P., & Engberg, J. (2026). Re-establishing bile acid composition after treatment of recurrent Clostridioides difficile infection with fecal microbiota transplantation compared with oral vancomycin or a 12-strain bacterial mixture. Gut Microbes, Article 2658915. https://doi.org/10.1080/19490976.2026.2658915