Analysis of data from a phase 3 clinical trial provides some clues as to how a microbiota-based treatment helps prevent recurrent Clostridioides difficile (rCDI) infection, researchers reported yesterday in the Journal of Infectious Diseases.
For the study, researchers analyzed stool samples from participants in PUNCH CD3, a randomized clinical trial that found the fecal microbiota-based live biotherapeutic Rebyota (RBL) was clinically superior to placebo in preventing rCDI. The researchers wanted to investigate the extent to which RBL restores the balance of bacteria and bile acid (BA) in the gut microbiome following antibiotic therapy, which is typically the first line of treatment for rCDI patients but often causes further gut microbiome disruption and increases the risk of future recurrence.
RBL linked to microbiota, BA changes
Stool samples were collected from participants who received a dose of RBL or placebo at baseline and 1, 4, and 8 weeks after treatment. Sequencing of those samples revealed that, before administration, Gammaproteobacteria and Bacilli dominated the microbiota community, and primary BAs were more prevalent than secondary BAs in trial participants. These characteristics are associated with reduced resistance to C difficile colonization, the study authors note.
“Thus, trial participants were dysbiotic before study treatment in ways that could enable CDI recurrence,” they wrote.
In participants who responded to treatment with RBL or placebo, clinical success after administration correlated with shifts to predominantly Bacteroidia and Clostridia, a significant increase in the Microbiome Health Index, and a shift from primary to secondary BAs. But several microbiota and BA changes were more extensive in RBL-treated responders than in placebo-treated responders, and microbiota changes correlated with BA changes.
“Overall, the microbiome and BA analyses herein support a model in which Bacteroidia restoration, decreased Gammaproteobacteria levels, and the increased metabolism of primary to secondary BAs were potential drivers of RBL clinical efficacy,” the authors concluded.
RBL was approved by the US Food and Drug Administration for the prevention of rCDI in 2022 based on data from PUNCH CD3 and other clinical trials.
