Faecalibacterium prausnitzii EXL01 Strain for the Prevention of Multiple-Recurrent Clostridioides difficile Infection
Year: 2026
Type: article
Study design: Clinical Trial
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).
Source: Gastroenterology
Authors: Nicolas Benech, Perle Guarino-Vignon, Paul McLellan, Camille Campidelli, Madeline Sergeant, Fanny Joubert, Sandrine Truong, Patricia Barbier, Emma Sandoz, Pauline Ruffié, Delphine Sedda, Alexiane Delmeule, Pierre Pradat, Cécilia Landman, Anne Bourrier, Léa Marchand, Laurent Alric, Julien Scanzi, Nadim Cassir, Amélie Dureault, Emilie Piet, Salomé Gallet, Elisabeth Botelho-Nevers, Tiphaine Roussel-Gaillard, Charlotte Cuerq, Florence Ader, Marielle Guillet, Nathalie Rolhion, Jean-Pierre Grill, Antonin Lamaziere, Jean-Marc Chatel, Séverine Pechine, Philippe Langella, Harry Sokol
Institutions: Lyon 1 Université, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Centre de Recherche en Cancérologie de Lyon, Inserm, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Centre de Recherche Saint-Antoine, Hôpital Saint-Antoine, AgroParisTech, Université Paris-Saclay, Microbiologie de l’alimentation au service de la santé, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Groupe Français de Transplantation Fécale, Hôpital Rangueil, Université de Toulouse, Aix-Marseille Université, Méditerranée Infection Foundation, Assistance Publique Hôpitaux de Marseille, Microbes Evolution Phylogénie et Infections, Centre Hospitalier de Valence, Centre Hospitalier Annecy Genevois, Centre Hospitalier Universitaire de Grenoble, Centre National de la Recherche Scientifique, Université de Lyon, Centre Hospitalier Universitaire de Saint-Étienne, Centre International de Recherche en Infectiologie, Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne, Université Jean Monnet, Laboratoire de recherche en cardiovasculaire, métabolisme, diabétologie et nutrition
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,180
OpenAlex ID: W7213470367