Impact of Live Biotherapeutic Products on Gut Microbiome in Recurrent C difficile Infections


Presented at DDW 2024 by Ken Blount, the effectiveness of live biotherapeutic products in treating recurrent C difficile infections (rCDI), offering insights into microbiota alteration and prospects for management.

Kenn Blount PhD, Chief Scientific Officer at Rebiotix and VP Microbiome Research at Ferring Pharmaceuticals

Ken Blount, VP Microbiome Research, Ferring.

Live biotherapeutic products have emerged as potential innovators in altering the gut microbiome of recipients. Specifically, fecal microbiota, notably live-jslm (RBL), has gained attention as the first FDA-approved, single-dose treatment for preventing recurrent C difficile infections (rCDIs) in adults with poststandard antibiotic therapy. This analysis showcased the transfer, colonization, and enduring presence of clonal populations from RBL to recipients, emphasizing the correlation between engraftment and clinical response, thus highlighting its role in microbiome restoration post-RBL administration.

The PUNCH CD3 trial, led by researcher Ken Blount, PhD, vice president of Microbiome Research, Ferring, discusses the efficacy and safety of RBL in preventing rCDI among adults 18 and older with a history of rCDI.

“In this exploratory analysis of the PUNCH CD3 trial, we did see significantly more engrafted species in clinical responders than in non-responders, with clinical response defined as the absence of CDI recurrence at 8 weeks after RBL administration,” Blount explained. “This subgroup comparison was conducted with samples provided within one week after RBL administration, during the established window when patients are thought to be most vulnerable to recurrence.”

Participants who received RBL and successfully avoided CDI recurrence at the 8-week mark experienced an improvement in their gut microbiota composition and diversity within just 1 week postadministration. A median of 10 species (ranging from 0 to 78) had been transferred from RBL to the participants through clonal engraftment. Stool samples collected from participants at various intervals underwent deep shotgun sequencing, revealing insights into microbiome composition and engraftment dynamics.

Notably, participants who achieved treatment success at 8 weeks exhibited a shift towards a healthier gut microbiota within just one week of RBL administration. This shift correlated with the clonal engraftment of a median of 10 species from RBL to participants.

Blount continued, “Our approach to engraftment analysis began by comparing the gut microbiome of trial participants post-RBL administration with the species present in the RBL dose they received. If sufficient variant loci shared identical sequences between the participant and the RBL dose, it indicated that the species in the participant originated from or engrafted from the RBL dose. This method, aligned with traditional medical understanding of stem-cell engraftment, aims to precisely elucidate how RBL influences the microbiome. We believe this approach provides a clearer definition of engraftment in the context of microbiota-based therapeutics and establishes a leading method for assessing engraftment in rCDI patients."

“Our next steps are to evaluate how engraftment may have shaped the overall microbiome and metabolome structure in ways that may also correlate with clinical efficacy,” Blount concludes.

Blount K, Claypool J, Ward T, et. al. Significant and Durable Microbiome Compositional Changes and Clonal Engraftment in a Phase 3 Trial of Fecal Microbiota, Live-JSLM for Recurrent Clostridioides difficile Infection. Digestive Disease Week (DDW). May 18-21, 2024 Washington DC.
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