Reintroducing virulent viruses to synthetic microbiomes

An emerging area of interest is how virulent viruses impact the assembly, structure, and function of commensal bacterial populations in the human gut. Synthetic microbiomes offer a powerful way to study these interactions in vitro, however, a major challenge is obtaining a representative bacteriophage population during the isolation process. Here, we demonstrate that standard colony isolation procedures reliably exclude virulent viruses from synthetic microbiomes. When the virulent virome was reintroduced to a 73-strain synthetic microbiome and cocultured in a bioreactor model of the human colon, we found that phage predation had a targeted effect on susceptible strains, but little overall impact on community structure and metabolism. Overall, the findings indicate that dilution-based isolation methods are prone to generating synthetic microbiomes heavily depleted, if not devoid, of virulent viruses, and that those viruses, if reintroduced, impact community assembly, metabolism, and prophage induction.

当前一个备受关注的新兴研究方向，是烈性病毒（virulent viruses）对人类肠道内共生细菌群落（commensal bacterial populations）的组装、结构与功能产生的影响。合成微生物组（synthetic microbiomes）为体外（in vitro）研究这类相互作用提供了强有力的技术手段，但当前面临的一大核心挑战是，在分离流程中获取具有代表性的噬菌体（bacteriophage）群落。本研究证实，标准菌落分离程序可稳定地将烈性病毒从合成微生物组中排除。当将烈性病毒组（virulent virome）重新引入含73株菌的合成微生物组，并在人类结肠生物反应器模型中共培养时，我们发现噬菌体捕食作用仅对易感菌株产生靶向效应，而对群落整体结构与代谢几乎无影响。综上，本研究结果表明，基于稀释的分离方法极易导致合成微生物组被烈性病毒大量清除（即便未完全剔除）；而这类病毒若被重新引入，则会对群落组装、代谢以及原噬菌体诱导（prophage induction）产生影响。