Gut Dysbiosis during Influenza Contributes to Pulmonary Pneumococcal Superinfection through Altered Short-Chain Fatty Acid Production

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.

Read full text: Valentin Sencio, Adeline Barthelemy, Luciana P. Tavares, Marina G. Machado, Daphnée Soulard, Céline Cuinat, Celso Martins Queiroz-Junior, Marie-Louise Noordine, Sophie Salomé-Desnoulez, Lucie Deryuter, Benoit Foligné, Céline Wahl, Benoit Frisch, Angelica T. Vieira, Christophe Paget, Graeme Milligan, Trond Ulven, Isabelle Wolowczuk, Christelle Faveeuw, Ronan Le Goffic, Muriel Thomas, Stéphanie Ferreira, Mauro M. Teixeira, François Trottein, Gut Dysbiosis during Influenza Contributes to Pulmonary Pneumococcal Superinfection through Altered Short-Chain Fatty Acid Production, Cell Reports, Volume 30, Issue 9, 2020, Pages 2934-2947.e6, https://doi.org/10.1016/j.celrep.2020.02.013

Keywords: influenza A virus, bacterial superinfection, gut microbiota, microbial dysbiosis, food restriction, short-chain fatty acid, acetate, free fatty acid receptor 2, macrophages, #Microbiota, #ShortChainFattyAcids.

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