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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.
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https://hal-univ-tours.archives-ouvertes.fr/hal-03365051
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Submitted on : Monday, October 11, 2021 - 11:42:44 AM
Last modification on : Wednesday, October 20, 2021 - 12:25:05 AM

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Distributed under a Creative Commons Attribution - NoDerivatives 4.0 International License

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Valentin Sencio, Adeline Barthelemy, Luciana Tavares, Marina Machado, Daphnée Soulard, et al.. Gut Dysbiosis during Influenza Contributes to Pulmonary Pneumococcal Superinfection through Altered Short-Chain Fatty Acid Production. Cell Reports, Elsevier Inc, 2020, 30 (9), pp.2934-2947.e6. ⟨10.1016/j.celrep.2020.02.013⟩. ⟨hal-03365051⟩

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