Faecalibacterium prausnitzii EXL01 Strain for the prevention of multiple-recurrent Clostridioides difficile Infection
Abstract
BACKGROUND & AIMS: Recurrent Clostridioides difficile infection (CDI) results from persistent microbiome dysfunction and impaired colonization resistance. Although fecal microbiota transplantation (FMT) is effective, defined and scalable alternatives are needed. We evaluated whether a single commensal strain could restore key microbiome functions and prevent recurrence. METHODS: We assessed Faecalibacterium prausnitzii EXL01 in a murine CDI model and a multicenter, open-label single-arm phase 1 trial including adults with ≥3 CDI episodes. Following vancomycin preconditioning, patients received oral EXL01 for 8 weeks with 8-week follow-up. Primary endpoint was safety. Secondary endpoints included recurrence at week 8. Longitudinal stool samples underwent shotgun metagenomics and metabolomics. Outcomes were benchmarked against matched FMT cohorts. Additional in vitro and murine studies of EXL01 were performed. RESULTS: In mice, EXL01 reduced C difficile burden and intestinal inflammation in an antibiotic-disrupted murine model. Six patients were treated; no treatment-related serious adverse events occurred. Five of 6 patients (83.3%) remained recurrence-free at week 8, comparable to matched FMT cohorts. EXL01 was detectable in stool up to 8 weeks post treatment. Multi-omics analyses showed that EXL01 engraftment was correlated with restoration of bile acid metabolism, including reduced primary bile acids and increased secondary bile acids, and increased short-chain fatty acid production, particularly butyrate, despite limited taxonomic recovery. EXL01 selectively deconjugated bile acids in vitro. CONCLUSIONS: A single, well-characterized bacterial strain was associated with restoration of key microbiome functions and low recurrence rates in high-risk recurrent CDI. These findings support precision microbiome therapeutics targeting ecosystem function rather than taxonomic complexity. Controlled trials are ongoing. (ClinicalTrials.gov, Number: NCT06306014).
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BibTeX
@article{benech2026faecalibacterium,
title = {{Faecalibacterium prausnitzii EXL01 Strain for the prevention of multiple-recurrent Clostridioides difficile Infection}},
author = {Nicolas Benech and Perle Guarino-Vignon and Paul Mclellan and Camille Campidelli and Madeline Sergeant and Fanny Joubert and Sandrine Truong and Patricia Barbier and Emma Sandoz and Pauline Ruffié and Delphine Sedda and Alexiane Delmeule and Pierre Pradat and Cécilia Landman and Anne Bourrier and Léa Marchand and Laurent Alric and Julien Scanzi and Nadim Cassir and Amélie Dureault and Emilie Piet and Salomé Gallet and Elisabeth Botelho-Nevers and Tiphaine Roussel-Gaillard and Charlotte Cuerq and Florence Ader and Marielle Guillet and Nathalie Rolhion and Jean-Pierre Grill and Antonin Lamaziere and Jean-Marc Chatel and Séverine Pechine and Philippe Langella and Harry Sokol},
journal = {Gastroenterology},
year = {2026},
month = oct,
doi = {10.1053/j.gastro.2026.09.002},
url = {https://hal.science/hal-05783919v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Faecalibacterium prausnitzii EXL01 Strain for the prevention of multiple-recurrent Clostridioides difficile Infection
AU - Nicolas Benech
AU - Perle Guarino-Vignon
AU - Paul Mclellan
AU - Camille Campidelli
AU - Madeline Sergeant
AU - Fanny Joubert
AU - Sandrine Truong
AU - Patricia Barbier
AU - Emma Sandoz
AU - Pauline Ruffié
AU - Delphine Sedda
AU - Alexiane Delmeule
AU - Pierre Pradat
AU - Cécilia Landman
AU - Anne Bourrier
AU - Léa Marchand
AU - Laurent Alric
AU - Julien Scanzi
AU - Nadim Cassir
AU - Amélie Dureault
AU - Emilie Piet
AU - Salomé Gallet
AU - Elisabeth Botelho-Nevers
AU - Tiphaine Roussel-Gaillard
AU - Charlotte Cuerq
AU - Florence Ader
AU - Marielle Guillet
AU - Nathalie Rolhion
AU - Jean-Pierre Grill
AU - Antonin Lamaziere
AU - Jean-Marc Chatel
AU - Séverine Pechine
AU - Philippe Langella
AU - Harry Sokol
PY - 2026
DA - 2026/10/07
JO - Gastroenterology
DO - 10.1053/j.gastro.2026.09.002
UR - https://hal.science/hal-05783919v1
AB - BACKGROUND & AIMS: Recurrent Clostridioides difficile infection (CDI) results from persistent microbiome dysfunction and impaired colonization resistance. Although fecal microbiota transplantation (FMT) is effective, defined and scalable alternatives are needed. We evaluated whether a single commensal strain could restore key microbiome functions and prevent recurrence. METHODS: We assessed Faecalibacterium prausnitzii EXL01 in a murine CDI model and a multicenter, open-label single-arm phase 1 trial including adults with ≥3 CDI episodes. Following vancomycin preconditioning, patients received oral EXL01 for 8 weeks with 8-week follow-up. Primary endpoint was safety. Secondary endpoints included recurrence at week 8. Longitudinal stool samples underwent shotgun metagenomics and metabolomics. Outcomes were benchmarked against matched FMT cohorts. Additional in vitro and murine studies of EXL01 were performed. RESULTS: In mice, EXL01 reduced C difficile burden and intestinal inflammation in an antibiotic-disrupted murine model. Six patients were treated; no treatment-related serious adverse events occurred. Five of 6 patients (83.3%) remained recurrence-free at week 8, comparable to matched FMT cohorts. EXL01 was detectable in stool up to 8 weeks post treatment. Multi-omics analyses showed that EXL01 engraftment was correlated with restoration of bile acid metabolism, including reduced primary bile acids and increased secondary bile acids, and increased short-chain fatty acid production, particularly butyrate, despite limited taxonomic recovery. EXL01 selectively deconjugated bile acids in vitro. CONCLUSIONS: A single, well-characterized bacterial strain was associated with restoration of key microbiome functions and low recurrence rates in high-risk recurrent CDI. These findings support precision microbiome therapeutics targeting ecosystem function rather than taxonomic complexity. Controlled trials are ongoing. (ClinicalTrials.gov, Number: NCT06306014).
SN - 0016-5085
SN - 1528-0012
ER -