Impact of a purified microbiome therapeutic on abundance of antimicrobial resistance genes in patients with recurrent Clostridioides difficile infection.
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Issue Date
4/10/2024
Authors
Straub, Timothy J
Lombardo, Mary-Jane
Bryant, Jessica A
Diao, Liyang
Lodise, Thomas
Freedberg, Daniel E
Wortman, Jennifer
Litcofsky, Kevin D
Hasson, Brooke R
McGovern, Barbara H
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Abstract
Background: The gastrointestinal microbiota is an important line of defense against colonization with antimicrobial resistant (AR) bacteria. In this post hoc analysis of the Phase 3 ECOSPOR III trial, we assessed impact of a microbiota-based oral therapeutic (fecal microbiota spores, live [VOWSTTM Oral Spores; VOS, formerly SER-109]) compared with placebo, on AR gene (ARG) abundance in patients with recurrent Clostridioides difficile infection (rCDI).
Methods: Adults with rCDI were randomized to receive VOS or placebo orally for 3 days following standard-of-care antibiotics. ARG and taxonomic profiles were generated using whole metagenomic sequencing of stool at baseline and Weeks 1, 2, 8, and 24 post-treatment.
Results: Baseline (n=151) and serial post-treatment stool samples collected through 24 weeks (total n=472) from 182 patients (59.9% female; mean age 65.5 years) in ECOSPOR III as well as 68 stool samples obtained at a single timepoint from a healthy cohort were analyzed. Baseline ARG abundance was similar between arms and significantly elevated vs. the healthy cohort. By Week 1, there was a greater decline in ARG abundance in VOS vs. placebo (p=0.003) in association with marked decline of Proteobacteria and repletion of spore-forming Firmicutes, as compared with baseline. We observed abundance of Proteobacteria and non-spore forming Firmicutes were associated with ARG abundance, while spore-forming Firmicutes abundance was negatively associated.
Conclusions: This proof-of-concept analysis suggests that microbiome remodeling with Firmicutes spores may be a potential novel approach to reduce ARG colonization in the gastrointestinal tract.
Citation
Straub TJ, Lombardo MJ, Bryant JA, Diao L, Lodise TP, Freedberg DE, Wortman JR, Litcofsky KD, Hasson BR, McGovern BH, Ford CB, Henn MR. Impact of a Purified Microbiome Therapeutic on Abundance of Antimicrobial Resistance Genes in Patients With Recurrent Clostridioides difficile Infection. Clin Infect Dis. 2024 Apr 10;78(4):833-841. doi: 10.1093/cid/ciad636. PMID: 37823484; PMCID: PMC11006105.
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