Shotgun metagenomics and systemic targeted metabolomics highlight indole-3-propionic acid as a protective gut microbial metabolite against influenza infection.

Autor:	Heumel S; Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France., de Rezende Rodovalho V; Laboratory of Immunoinflammation, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Urien C; Genoscreen, Lille, France., Specque F; Biomathematica, Rue des Aloes, Quartier Balestrino, Ajaccio, France., Brito Rodrigues P; Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France.; Laboratory of Immunoinflammation, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Robil C; Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France., Delval L; Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France., Sencio V; Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France., Descat A; Univ. Lille, CHU Lille, EA 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, France., Deruyter L; Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France., Ferreira S; Genoscreen, Lille, France., Gomes Machado M; Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France., Barthelemy A; Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France., Angulo FS; Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France., Haas JT; Univ. Lille, INSERM, CHU Lille, Institut Pasteur de Lille, Lille, France., Goosens JF; Univ. Lille, CHU Lille, EA 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, France., Wolowczuk I; Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France., Grangette C; Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France., Rouillé Y; Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France., Grimaud G; Biomathematica, Rue des Aloes, Quartier Balestrino, Ajaccio, France., Lenski M; Univ. Lrille, CHU Lille, Service de toxicologie et Génopathies, ULR 4483 - IMPECS - IMPact de l'Environnement Chimique sur la Santé humaine, Lille, France., Hennart B; Univ. Lrille, CHU Lille, Service de toxicologie et Génopathies, ULR 4483 - IMPECS - IMPact de l'Environnement Chimique sur la Santé humaine, Lille, France., Ramirez Vinolo MA; Laboratory of Immunoinflammation, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Trottein F; Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France.
Jazyk:	angličtina
Zdroj:	Gut microbes [Gut Microbes] 2024 Jan-Dec; Vol. 16 (1), pp. 2325067. Date of Electronic Publication: 2024 Mar 06.
DOI:	10.1080/19490976.2024.2325067
Abstrakt:	The gut-to-lung axis is critical during respiratory infections, including influenza A virus (IAV) infection. In the present study, we used high-resolution shotgun metagenomics and targeted metabolomic analysis to characterize influenza-associated changes in the composition and metabolism of the mouse gut microbiota. We observed several taxonomic-level changes on day (D)7 post-infection, including a marked reduction in the abundance of members of the Lactobacillaceae and Bifidobacteriaceae families, and an increase in the abundance of Akkermansia muciniphila . On D14, perturbation persisted in some species. Functional scale analysis of metagenomic data revealed transient changes in several metabolic pathways, particularly those leading to the production of short-chain fatty acids (SCFAs), polyamines, and tryptophan metabolites. Quantitative targeted metabolomics analysis of the serum revealed changes in specific classes of gut microbiota metabolites, including SCFAs, trimethylamine, polyamines, and indole-containing tryptophan metabolites. A marked decrease in indole-3-propionic acid (IPA) blood level was observed on D7. Changes in microbiota-associated metabolites correlated with changes in taxon abundance and disease marker levels. In particular, IPA was positively correlated with some Lactobacillaceae and Bifidobacteriaceae species ( Limosilactobacillus reuteri, Lactobacillus animalis ) and negatively correlated with Bacteroidales bacterium M7, viral load, and inflammation markers. IPA supplementation in diseased animals reduced viral load and lowered local (lung) and systemic inflammation. Treatment of mice with antibiotics targeting IPA-producing bacteria before infection enhanced viral load and lung inflammation, an effect inhibited by IPA supplementation. The results of this integrated metagenomic-metabolomic analysis highlighted IPA as an important contributor to influenza outcomes and a potential biomarker of disease severity.
Databáze:	MEDLINE
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