Lactobacilli intra-tracheal administration protects from Pseudomonas aeruginosa pulmonary infection in mice – a proof of concept

Autor: S. Gouriou, M.-S. Fangous, D Arzur, Youenn Alexandre, Nolwenn Hymery, G Le Blay, R. Le Berre
Přispěvatelé: Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)
Rok vydání: 2019
Předmět:
Zdroj: Beneficial Microbes
Beneficial Microbes, Wageningen Academic Publishers 2019, 10 (8), pp.893-900. ⟨10.3920/BM2019.0069⟩
ISSN: 1876-2891
1876-2883
DOI: 10.3920/bm2019.0069
Popis: WOS:000501544400007; International audience; The spreading of antibiotic resistance is a major public health issue, which requires alternative treatments to antibiotics. Lactobacilli have shown abilities to prevent pneumonia in clinical studies when given by oral route, certainly through the gut-lung axis involvement. Rationally, respiratory administration of lactobacilli has been developed and studied in murine model, to prevent from respiratory pathogens. It allows a direct effect of probiotics into the respiratory system. To our knowledge, no study has ever focused on the effect of probiotic intra-respiratory administration to prevent from Pseudomonas aeruginosa (PA) pneumonia, a major respiratory pathogen associated with high morbidity rates. In this study, we evaluated the beneficial activity of three Lactobacillus strains (Lactobacillus fermentum K.C6.3.1E, Lactobacillus zeae Od.76, Lactobacillus paracasei ES.D.88) previously screened by ourselves and known to be particularly efficient in vitro in inhibiting PAO1 virulence factors. Cytotoxic assays in alveolar epithelial cell line A549 were performed, followed by the comparison of two lactobacilli prophylactic protocols (one or two administrations) by intra-tracheal administration in a C57BL/6 murine model of PA pneumonia. A549 cells viability was improved from 23 to 75% when lactobacilli were administered before PAO1 incubation, demonstrating a protective effect (P\textless0.001). A significant decrease of 2 log of PAO1 was observed 4 h after PAO1 instillation (3x 10(6) cfu/mouse) in both groups receiving lactobacilli (9x 10(6) cfu/mouse) compared to PAO1 group (P\textless0.05). One single prophylactic administration of lactobacilli significantly decreased the secretion by 50% in bronchoalveolar lavages of interleukin (IL)-6 and tumour necrosis factor-a compared to PAO1. No difference of secretion was observed for the IL-10 secretion, whatever the prophylactic study design. This is the first study highlighting that direct lung administration of Lactobacillus strains protect against PA pneumonia. Next step will be to decipher the mechanisms involved before developing this novel approach for human applications.
Databáze: OpenAIRE