Gut dysbiosis during influenza contributes to pulmonary pneumococcal superinfection through altered short-chain fatty acid production

Sencio, V. et al. (2020) Gut dysbiosis during influenza contributes to pulmonary pneumococcal superinfection through altered short-chain fatty acid production. Cell Reports, 30(9), 2934-2947.e6. (doi: 10.1016/j.celrep.2020.02.013) (PMID:32130898)

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Abstract

Secondary bacterial infections often complicate viral respiratory infections. We hypothesize that perturbation of the gut microbiota during influenza A virus (IAV) infection might favor respiratory bacterial superinfection. Sublethal infection with influenza transiently alters the composition and fermentative activity of the gut microbiota in mice. These changes are attributed in part to reduced food consumption. Fecal transfer experiments demonstrate that the IAV-conditioned microbiota compromises lung defenses against pneumococcal infection. In mechanistic terms, reduced production of the predominant short-chain fatty acid (SCFA) acetate affects the bactericidal activity of alveolar macrophages. Following treatment with acetate, mice colonized with the IAV-conditioned microbiota display reduced bacterial loads. In the context of influenza infection, acetate supplementation reduces, in a free fatty acid receptor 2 (FFAR2)-dependent manner, local and systemic bacterial loads. This translates into reduced lung pathology and improved survival rates of double-infected mice. Lastly, pharmacological activation of the SCFA receptor FFAR2 during influenza reduces bacterial superinfection.

Item Type:Articles
Additional Information:This work was supported in part by the INSERM, CNRS, University of Lille, Pasteur Institute of Lille, région des Hauts-de-France, state of Minais Gerais/FAPEMIG (Franco-Brazilian call 2014-2015, FLUMICROBIOT) (FT and MT), Innovation Fund Denmark grant 0603- 00452B (TU), Biotechnology and Biosciences Research Council grant BB/S000453/1 (GM), and Agence Nationale de la Recherche (ANR-17-CE15-0020-01, ACROBAT) (FT). VS and AB received salary support (PhD fellowship) by Lille University and by the Fondation pour la Recherche Médicale (VS).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Milligan, Professor Graeme
Authors: Sencio, V., Barthelemy, A., Tavares, L. P., Machado, M. G., Soulard, D., Cuinat, C., Queiroz-Junior, C. M., Noordine, M. L., Salomé-Desnoulez, S., Deryuter, L., Foligné, B., Wahl, C., Frisch, B., Vieira, A. T., Paget, C., Milligan, G., Ulven, T., Wolowczuk, I., Faveeuw, C., Le Goffic, R., Thomas, M., Ferreira, S., Teixeira, M. M., and Trottein, F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Cell Reports
Publisher:Elsevier (Cell Press)
ISSN:2211-1247
ISSN (Online):2211-1247
Published Online:03 March 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Cell Reports 30(9): 2934-2947.e6
Publisher Policy:Reproduced under a Creative Commons license

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