Respiratory viral infections are extremely common, but their impacts on the composition and function of the gut microbiota are poorly understood. We previously observed a significant change in the gut microbiota after viral lung infection. Here, we show that weight loss during respiratory syncytial virus (RSV) or influenza virus infection was due to decreased food consumption, and that the fasting of mice altered gut microbiota composition independently of infection. While the acute phase tumor necrosis factor alpha (TNF-α) response drove early weight loss and inappetence during RSV infection, this was not sufficient to induce changes in the gut microbiota. However, the depletion of CD8+ cells increased food intake and prevented weight loss, resulting in a reversal of the gut microbiota changes normally observed during RSV infection. Viral infection also led to changes in the fecal gut metabolome, with a significant shift in lipid metabolism. Sphingolipids, polyunsaturated fatty acids (PUFAs), and the short-chain fatty acid (SCFA) valerate were all increased in abundance in the fecal metabolome following RSV infection. Whether this and the impact of infection-induced anorexia on the gut microbiota are part of a protective anti-inflammatory response during respiratory viral infections remains to be determined.IMPORTANCE The gut microbiota has an important role in health and disease: gut bacteria can generate metabolites that alter the function of immune cells systemically. Understanding the factors that can lead to changes in the gut microbiome may help to inform therapeutic interventions. This is the first study to systematically dissect the pathway of events from viral lung infection to changes in gut microbiota. We show that the cellular immune response to viral lung infection induces inappetence, which in turn alters the gut microbiome and metabolome. Strikingly, there was an increase in lipids that have been associated with the resolution of disease. This opens up new paths of investigation: first, what is the (presumably secreted) factor made by the T cells that can induce inappetence? Second, is inappetence an adaptation that accelerates recovery from infection, and if so, does the microbiome play a role in this?

中文翻译：

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呼吸道病毒感染通过引起食欲不振来改变肠道微生物群。


呼吸道病毒感染极为常见，但人们对它们对肠道微生物群的组成和功能的影响知之甚少。我们之前观察到病毒性肺部感染后肠道微生物群发生了显着变化。在这里，我们发现呼吸道合胞病毒（RSV）或流感病毒感染期间体重减轻是由于食物消耗减少所致，并且小鼠的禁食改变了肠道微生物群的组成，而与感染无关。虽然急性期肿瘤坏死因子 α (TNF-α) 反应导致 RSV 感染期间早期体重减轻和食欲不振，但这不足以引起肠道微生物群的变化。然而，CD8+细胞的消耗增加了食物摄入量并阻止了体重减轻，导致RSV感染期间通常观察到的肠道微生物群变化发生逆转。病毒感染还导致粪便肠道代谢组的变化，脂质代谢发生显着变化。 RSV 感染后，粪便代谢组中的鞘脂、多不饱和脂肪酸 (PUFA) 和短链脂肪酸 (SCFA) 戊酸酯均丰度增加。这以及感染引起的厌食对肠道微生物群的影响是否是呼吸道病毒感染期间保护性抗炎反应的一部分仍有待确定。重要性肠道微生物群在健康和疾病中具有重要作用：肠道细菌可以产生代谢物系统性地改变免疫细胞的功能。了解可能导致肠道微生物组变化的因素可能有助于为治疗干预提供信息。这是第一项系统剖析从病毒性肺部感染到肠道微生物群变化的事件途径的研究。 我们发现，对病毒性肺部感染的细胞免疫反应会导致食欲不振，进而改变肠道微生物组和代谢组。引人注目的是，血脂的增加与疾病的消退有关。这开辟了新的研究途径：首先，T细胞产生的（大概是分泌的）因子是什么，可以引起食欲不振？其次，食欲不振是否是一种加速感染恢复的适应，如果是，微生物组是否在其中发挥作用？