The microbiota–gut–brain axis has been shown to play an important role in the stress response, but previous work has focused primarily on the role of the bacteriome. The gut virome constitutes a major portion of the microbiome, with bacteriophages having the potential to remodel bacteriome structure and activity. Here we use a mouse model of chronic social stress, and employ 16S rRNA and whole metagenomic sequencing on faecal pellets to determine how the virome is modulated by and contributes to the effects of stress. We found that chronic stress led to behavioural, immune and bacteriome alterations in mice that were associated with changes in the bacteriophage class Caudoviricetes and unassigned viral taxa. To determine whether these changes were causally related to stress-associated behavioural or physiological outcomes, we conducted a faecal virome transplant from mice before stress and autochthonously transferred it to mice undergoing chronic social stress. The transfer of the faecal virome protected against stress-associated behaviour sequelae and restored stress-induced changes in select circulating immune cell populations, cytokine release, bacteriome alterations and gene expression in the amygdala. These data provide evidence that the virome plays a role in the modulation of the microbiota–gut–brain axis during stress, indicating that these viral populations should be considered when designing future microbiome-directed therapies.

微生物群-肠-脑轴已被证明在应激反应中发挥着重要作用，但之前的工作主要集中在细菌组的作用上。肠道病毒组构成微生物组的主要部分，噬菌体具有重塑细菌组结构和活性的潜力。在这里，我们使用慢性社会压力的小鼠模型，并对粪便颗粒进行 16S rRNA 和全宏基因组测序，以确定病毒组如何受到压力的调节和影响。我们发现，慢性压力会导致小鼠行为、免疫和细菌组的改变，这些改变与噬菌体类有尾病毒和未分配的病毒类群的变化有关。为了确定这些变化是否与压力相关的行为或生理结果有因果关系，我们对压力前的小鼠进行了粪便病毒组移植，并将其自然转移到承受慢性社会压力的小鼠体内。粪便病毒组的转移可以防止应激相关的行为后遗症，并恢复应激诱导的选定循环免疫细胞群的变化、细胞因子的释放、细菌组的改变和杏仁核中的基因表达。这些数据提供了证据，表明病毒组在应激期间调节微生物群-肠-脑轴中发挥作用，表明在设计未来的微生物组导向疗法时应考虑这些病毒群。