Microbiome compositional changes and clonal engraftment in a phase 3 trial of fecal microbiota, live-jslm for recurrent Clostridioides difficile infection
Live microbiota therapies have shown promise in many gastrointestinal diseases, including in the prevention of recurrent Clostridioides difficile infections (rCDI); however, frameworks for their pharmacokinetic and pharmacodynamic analysis are not fully established. Fecal microbiota, live-jslm (RBL)...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2025.2520412 |
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| author | Josh Claypool Gustav Lindved Pernille Neve Myers Tonya Ward Henrik Bjørn Nielsen Ken F. Blount |
| author_facet | Josh Claypool Gustav Lindved Pernille Neve Myers Tonya Ward Henrik Bjørn Nielsen Ken F. Blount |
| author_sort | Josh Claypool |
| collection | DOAJ |
| description | Live microbiota therapies have shown promise in many gastrointestinal diseases, including in the prevention of recurrent Clostridioides difficile infections (rCDI); however, frameworks for their pharmacokinetic and pharmacodynamic analysis are not fully established. Fecal microbiota, live-jslm (RBL) is the first microbiota-based product approved by the US Food and Drug Administration for the prevention of rCDI and was superior to placebo in the PUNCH™ CD3 phase 3 clinical trial (NCT03244644). In this analysis, deep shotgun metagenomic sequencing was used to assess changes in gut microbiome compositions of participants and engraftment of bacterial clonal populations (i.e. strains) from RBL to recipients. Among RBL responders, gut microbiota shifted toward compositions that resembled healthy donors as early as 1 week after RBL administration; the resulting microbiota compositions included clonal populations that engrafted from RBL to recipients. Engraftment was higher in RBL responders compared with non-responders, and many clonally engrafted populations persisted for ≥ 6 months. Bacteroidia species were among the most effectively engrafted species from RBL. This study utilizes data from a large clinical trial to establish a method with high specificity for exploring clonal engraftment from microbiota-based treatments to facilitate future pharmacokinetic and pharmacodynamic analyses.Clinicaltrials Registration: NCT03244644 |
| format | Article |
| id | doaj-art-da8d2abb1ea1492192d1241a829cf14b |
| institution | OA Journals |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-da8d2abb1ea1492192d1241a829cf14b2025-08-20T02:21:17ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2520412Microbiome compositional changes and clonal engraftment in a phase 3 trial of fecal microbiota, live-jslm for recurrent Clostridioides difficile infectionJosh Claypool0Gustav Lindved1Pernille Neve Myers2Tonya Ward3Henrik Bjørn Nielsen4Ken F. Blount5Ferring Microbiome, Inc, Roseville, MN, USAClinical Microbiomics A/S, Copenhagen, DenmarkClinical Microbiomics A/S, Copenhagen, DenmarkFerring Microbiome, Inc, Roseville, MN, USAClinical Microbiomics A/S, Copenhagen, DenmarkFerring Microbiome, Inc, Roseville, MN, USALive microbiota therapies have shown promise in many gastrointestinal diseases, including in the prevention of recurrent Clostridioides difficile infections (rCDI); however, frameworks for their pharmacokinetic and pharmacodynamic analysis are not fully established. Fecal microbiota, live-jslm (RBL) is the first microbiota-based product approved by the US Food and Drug Administration for the prevention of rCDI and was superior to placebo in the PUNCH™ CD3 phase 3 clinical trial (NCT03244644). In this analysis, deep shotgun metagenomic sequencing was used to assess changes in gut microbiome compositions of participants and engraftment of bacterial clonal populations (i.e. strains) from RBL to recipients. Among RBL responders, gut microbiota shifted toward compositions that resembled healthy donors as early as 1 week after RBL administration; the resulting microbiota compositions included clonal populations that engrafted from RBL to recipients. Engraftment was higher in RBL responders compared with non-responders, and many clonally engrafted populations persisted for ≥ 6 months. Bacteroidia species were among the most effectively engrafted species from RBL. This study utilizes data from a large clinical trial to establish a method with high specificity for exploring clonal engraftment from microbiota-based treatments to facilitate future pharmacokinetic and pharmacodynamic analyses.Clinicaltrials Registration: NCT03244644https://www.tandfonline.com/doi/10.1080/19490976.2025.2520412CDIClostridioides difficiledysbiosismicrobiota-based productengraftmentpharmacokinetics |
| spellingShingle | Josh Claypool Gustav Lindved Pernille Neve Myers Tonya Ward Henrik Bjørn Nielsen Ken F. Blount Microbiome compositional changes and clonal engraftment in a phase 3 trial of fecal microbiota, live-jslm for recurrent Clostridioides difficile infection Gut Microbes CDI Clostridioides difficile dysbiosis microbiota-based product engraftment pharmacokinetics |
| title | Microbiome compositional changes and clonal engraftment in a phase 3 trial of fecal microbiota, live-jslm for recurrent Clostridioides difficile infection |
| title_full | Microbiome compositional changes and clonal engraftment in a phase 3 trial of fecal microbiota, live-jslm for recurrent Clostridioides difficile infection |
| title_fullStr | Microbiome compositional changes and clonal engraftment in a phase 3 trial of fecal microbiota, live-jslm for recurrent Clostridioides difficile infection |
| title_full_unstemmed | Microbiome compositional changes and clonal engraftment in a phase 3 trial of fecal microbiota, live-jslm for recurrent Clostridioides difficile infection |
| title_short | Microbiome compositional changes and clonal engraftment in a phase 3 trial of fecal microbiota, live-jslm for recurrent Clostridioides difficile infection |
| title_sort | microbiome compositional changes and clonal engraftment in a phase 3 trial of fecal microbiota live jslm for recurrent clostridioides difficile infection |
| topic | CDI Clostridioides difficile dysbiosis microbiota-based product engraftment pharmacokinetics |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2025.2520412 |
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