Gut Dysbiosis during Influenza Contributes to Pulmonary Pneumococcal Superinfection through Altered Short-Chain Fatty Acid Production
Gut Dysbiosis during Influenza Contributes to Pulmonary Pneumococcal Superinfection through Altered Short-Chain Fatty Acid Production
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DOI：
10.1016/j.celrep.2020.02.013
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发表时间：
2020-03-03
期刊：
影响因子：
8.8
通讯作者：
Trottein, Francois
中科院分区：
文献类型：
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作者：
Sencio, Valentin;Barthelemy, Adeline;Trottein, Francois
继发性细菌感染往往使病毒性呼吸道感染复杂化。我们推测，在甲型流感病毒(IAV)感染期间，肠道微生物区系的扰动可能有利于呼吸道细菌的重叠感染。流感的亚致死性感染会暂时改变小鼠肠道微生物区系的组成和发酵活动。这些变化在一定程度上归因于食物消费的减少。粪便转移实验表明，IAV条件下的微生物群损害了肺对肺炎球菌感染的防御。从机理上讲，主要的短链脂肪酸(SCFA)醋酸酯的减少会影响肺泡巨噬细胞的杀菌活性。在醋酸盐处理后，用IAV条件微生物区系定植的小鼠表现出较低的细菌负荷。在流感感染的背景下，醋酸盐补充剂以游离脂肪酸受体2(FFAR2)依赖的方式减少局部和全身细菌负荷。这可以减少肺部病理，提高双重感染小鼠的存活率。最后，在流感期间，SCFA受体FFAR2的药理激活减少了细菌的重叠感染。
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.