Safety and Efficacy of an AIEC-targeted Bacteriophage Cocktail in a Mice Colitis Model. - Université de Lille Accéder directement au contenu
Article Dans Une Revue Journal of Crohn's and Colitis Année : 2022

Safety and Efficacy of an AIEC-targeted Bacteriophage Cocktail in a Mice Colitis Model.

Résumé

Background and aims Adherent invasive Escherichia coli [AIEC] are recovered with a high frequency from the gut mucosa of Crohn’s disease patients and are believed to contribute to the dysbiosis and pathogenesis of this inflammatory bowel disease. In this context, bacteriophage therapy has been proposed for specifically targeting AIEC in the human gut with no deleterious impact on the commensal microbiota. Methods The in vitro efficacy and specificity of a seven lytic phage cocktail [EcoActive™] was assessed against [i] 210 clinical AIEC strains, and [ii] 43 non-E. coli strains belonging to the top 12 most common bacterial genera typically associated with a healthy human microbiome. These data were supported by in vivo safety and efficacy assays conducted on healthy and AIEC-colonized mice, respectively. Results The EcoActive cocktail was effective in vitro against 95% of the AIEC strains and did not lyse any of the 43 non-E. coli commensal strains, in contrast to conventional antibiotics. Long-term administration of the EcoActive cocktail to healthy mice was safe and did not induce dysbiosis according to metagenomic data. Using a murine model of induced colitis of animals infected with the AIEC strain LF82, we found that a single administration of the cocktail failed to alleviate inflammatory symptoms, while mice receiving the cocktail twice a day for 15 days were protected from clinical and microscopical manifestations of inflammation. Conclusions Collectively, the data support the approach of AIEC-targeted phage therapy as safe and effective treatment for reducing AIEC levels in the gut of IBD patients.

Mots clés

Dates et versions

hal-04426439 , version 1 (30-01-2024)

Identifiants

Citer

Marie Titecat, Christel Rousseaux, Caroline Dubuquoy, Benoit Foligne, Oumaira Rahmouni, et al.. Safety and Efficacy of an AIEC-targeted Bacteriophage Cocktail in a Mice Colitis Model.. Journal of Crohn's and Colitis, 2022, Journal of Crohn's and Colitis, 16 (10), pp.1617-1627. ⟨10.1093/ecco-jcc/jjac064⟩. ⟨hal-04426439⟩
15 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More