Nature：肠道病毒，细菌对抗抗生素的同盟军

如今，抗生素滥用现象使耐药菌日渐增多，目前这已经成为了一个全球性的公共健康问题。过去，人们在研究肠道菌对抗生素的适应性时，往往只针对细菌本身。

现在，波士顿大学等机构的科学家发现，当肠道菌受到抗生素攻击时，肠道内的病毒会成为它们的同盟军，使细菌快速产生对药物的抗性。

这些被称为噬菌体的肠道病毒，能够在细菌间传递基因，由此帮助细菌在抗生素的攻击下存活。能够抵抗多种抗生素的细菌被称为超级菌，而这项研究显示，肠道中的噬菌体加速了超级菌的出现。研究人员指出，靶标噬菌体的药物有望成为阻击超级菌的新途径。

在这项研究中，科学家对肠道内的噬菌体进行了分析，噬菌体在肠道内丰度很高，而且它们很擅长在细菌之间运输基因。

研究人员分别用环丙沙星和氨苄青霉素两种抗生素处理小鼠，并于 8 周后收获小鼠排泄物中的所有病毒。他们对这些病毒的基因进行鉴定，将其与大型的基因数据库进行比对。研究人员发现，与对照组相比，抗生素处理组的噬菌体携带更多的细菌耐药基因。

此外，氨苄处理组的噬菌体，携带的基因主要有助于细菌抵抗氨苄等青霉素。而环丙沙星处理组的噬菌体，携带的基因主要是帮助细菌抵抗环丙沙星及相关药物。

研究显示，噬菌体不仅携带耐药基因，还会将这些基因转移给肠道菌，赋予细菌耐药性。研究人员分别从抗生素处理组和对照组小鼠体内分离噬菌体，然后将这些噬菌体添加到未受抗生素处理的肠道菌中。他们发现，氨苄处理组的噬菌体，使肠道菌的氨苄抗性增加到三倍，而环丙沙星处理组的噬菌体，使肠道菌的环丙沙星抗性增加到两倍。不仅如此，经一种抗生素处理的肠道噬菌体，可以通过基因赋予细菌对其他药物的抗性。

研究人员指出，上述发现为解决细菌耐药问题，开辟了一条全新的途径。人们可以通过靶标肠道中的噬菌体，来延缓细菌对抗生素产生抗性。

Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome
Abstract
The mammalian gut ecosystem has considerable influence on host physiology1, 2, 3, 4, but the mechanisms that sustain this complex environment in the face of different stresses remain obscure. Perturbations to the gut ecosystem, such as through antibiotic treatment or diet, are at present interpreted at the level of bacterial phylogeny5, 6, 7. Less is known about the contributions of the abundant population of phages to this ecological network. Here we explore the phageome as a potential genetic reservoir for bacterial adaptation by sequencing murine faecal phage populations following antibiotic perturbation. We show that antibiotic treatment leads to the enrichment of phage-encoded genes that confer resistance via disparate mechanisms to the administered drug, as well as genes that confer resistance to antibiotics unrelated to the administered drug, and we demonstrate experimentally that phages from treated mice provide aerobically cultured naive microbiota with increased resistance. Systems-wide analyses uncovered post-treatment phage-encoded processes related to host colonization and growth adaptation, indicating that the phageome becomes broadly enriched for functionally beneficial genes under stress-related conditions. We also show that antibiotic treatment expands the interactions between phage and bacterial species, leading to a more highly connected phage–bacterial network for gene exchange. Our work implicates the phageome in the emergence of multidrug resistance, and indicates that the adaptive capacity of the phageome may represent a community-based mechanism for protecting the gut microflora, preserving its functional robustness during antibiotic stress.