Reduction of product composition variability using pooled microbiome ecosystem therapy and consequence in two infectious murine models
2024
Reygner, Julie | Delannoy, Johanne | Barba-Goudiaby, Marie-Thérèse | Gasc, Cyrielle | Levast, Benoît | Gaschet, Enora | Ferraris, Laurent | Paul, Stéphane | Kapel, Nathalie | Waligora-Dupriet, Anne-Judith | Barbut, Frederic | Thomas, Muriel | Schwintner, Carole | Laperrousaz, Bastien | Corvaïa, Nathalie | MaaT Pharma [Lyon] | Physiopathologie et pharmacotoxicologie placentaire humaine : Microbiote pré & post natal (3PHM - UMR-S 1139) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité) | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Université Jean Monnet - Saint-Étienne (UJM) | Physiopathologie et biothérapies des infections muqueuses [CIRI] (CIRI-GIMAP) ; Centre International de Recherche en Infectiologie (CIRI) ; École normale supérieure de Lyon (ENS de Lyon) ; Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon) ; Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) | Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E) | Centre d'Investigation Clinique - Epidémiologie Clinique [CHU Saint-Etienne] (CIC-EC 1408) ; Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon | Laboratoire de Coprologie Fonctionnelle ; CHU Pitié-Salpêtrière [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) | CHU Saint-Antoine [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) | European Society of Clinical Microbiology and Infectious Diseases Study Group for Clostridioides difficile | MaaT Pharma
International audience
显示更多 [+] 显示较少 [-]英语. Growing evidence demonstrates the key role of the gut microbiota in human health and disease. The recent success of microbiotherapy products to treat recurrent Clostridioides difficile infection has shed light on its potential in conditions associated with gut dysbiosis, such as acute graft-versus-host disease, intestinal bowel diseases, neurodegenerative diseases, or even cancer. However, the difficulty in defining a “good” donor as well as the intrinsic variability of donor-derived products’ taxonomic composition limits the translatability and reproducibility of these studies. Thus, the pooling of donors’ feces has been proposed to homogenize product composition and achieve higher taxonomic richness and diversity. In this study, we compared the metagenomic profile of pooled products to corresponding single donor-derived products. We demonstrated that pooled products are more homogeneous, diverse, and enriched in beneficial bacteria known to produce anti-inflammatory short chain fatty acids compared to single donor-derived products. We then evaluated pooled products’ efficacy compared to corresponding single donor-derived products in Salmonella and C. difficile infectious mouse models. We were able to demonstrate that pooled products decreased pathogenicity by inducing a structural change in the intestinal microbiota composition. Single donor-derived product efficacy was variable, with some products failing to control disease progression. We further performed in vitro growth inhibition assays of two extremely drug-resistant bacteria, Enterococcus faecium vanA and Klebsiella pneumoniae oxa48, supporting the use of pooled microbiotherapies. Altogether, these results demonstrate that the heterogeneity of donor-derived products is corrected by pooled fecal microbiotherapies in several infectious preclinical models.
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