Infections elicit immune adaptations to enable pathogen resistance and/or tolerance and are associated with compositional shifts of the intestinal microbiome. However, a comprehensive understanding of how infections with pathogens that exhibit distinct capability to spread and/or persist differentially change the microbiome, the underlying mechanisms, and the relative contribution of individual commensal species to immune cell adaptations is still lacking. Here, we discovered that mouse infection with a fast-spreading and persistent (but not a slow-spreading acute) isolate of lymphocytic choriomeningitis virus induced large-scale microbiome shifts characterized by increased Verrucomicrobia and reduced Firmicute/Bacteroidetes ratio. Remarkably, the most profound microbiome changes occurred transiently after infection with the fast-spreading persistent isolate, were uncoupled from sustained viral loads, and were instead largely caused by CD8 T cell responses and/or CD8 T cell-induced anorexia. Among the taxa enriched by infection with the fast-spreading virus, Akkermansia muciniphila, broadly regarded as a beneficial commensal, bloomed upon starvation and in a CD8 T cell-dependent manner. Strikingly, oral administration of A. muciniphila suppressed selected effector features of CD8 T cells in the context of both infections. Our findings define unique microbiome differences after chronic versus acute viral infections and identify CD8 T cell responses and downstream anorexia as driver mechanisms of microbial dysbiosis after infection with a fast-spreading virus. Our data also highlight potential context-dependent effects of probiotics and suggest a model in which changes in host behavior and downstream microbiome dysbiosis may constitute a previously unrecognized negative feedback loop that contributes to CD8 T cell adaptations after infections with fast-spreading and/or persistent pathogens.

感染引发免疫适应以实现病原体抵抗和/或耐受，并与肠道微生物组的组成变化相关。然而，对于表现出独特的传播和/或持续能力的病原体感染如何差异性地改变微生物组、潜在机制以及单个共生物种对免疫细胞适应的相对贡献的全面了解仍然缺乏。在这里，我们发现，小鼠感染快速传播和持续（但不是缓慢传播的急性）淋巴细胞脉络膜脑膜炎病毒分离株会引起大规模的微生物组变化，其特征是疣微菌增加和厚壁菌门/拟杆菌门比率降低。值得注意的是，最深刻的微生物组变化在感染快速传播的持久性分离株后短暂发生，与持续的病毒载量无关，而是主要由 CD8 T 细胞反应和/或 CD8 T 细胞诱导的厌食症引起。在通过快速传播的病毒感染而丰富的类群中， Akkermansia muciniphila被广泛认为是一种有益的共生体，它在饥饿时以 CD8 T 细胞依赖性方式大量繁殖。引人注目的是，口服A. muciniphila抑制了两种感染情况下 CD8 T 细胞的选定效应特征。我们的研究结果定义了慢性与急性病毒感染后独特的微生物组差异，并确定 CD8 T 细胞反应和下游厌食症是快速传播的病毒感染后微生物失调的驱动机制。 我们的数据还强调了益生菌潜在的环境依赖性效应，并提出了一个模型，其中宿主行为的变化和下游微生物群失调可能构成一个先前未被认识的负反馈循环，该循环有助于 CD8 T 细胞在快速传播和/或持续感染后的适应病原体。