Despite an overall temporal stability in time of the human gut microbiota at the phylum level, strong variations in species abundance have been observed. We are far from a clear understanding of what promotes or disrupts the stability of microbiome communities. Environmental factors, like food or antibiotic use, modify the gut microbiota composition, but their overall impacts remain relatively low. Phages, the viruses that infect bacteria, might constitute important factors explaining temporal variations in species abundance. Gut bacteria harbour numerous prophages, or dormant viruses, which can evolve to become ultravirulent phage mutants, potentially leading to important bacterial death. Whether such phenomenon occurs in the mammal's microbiota has been largely unexplored. Here we studied temperate phage-bacteria coevolution in gnotoxenic mice colonised with Roseburia intestinalis, a dominant symbiont of the human gut microbiota, and Escherichia coli, a sub-dominant member of the same microbiota. We show that R. intestinalis L1-82 harbours two active prophages, Jekyll and Shimadzu. We observed the systematic evolution in mice of ultravirulent Shimadzu phage mutants, which led to a collapse of R. intestinalis population. In a second step, phage infection drove the fast counter-evolution of host phage resistance mainly through phage-derived spacer acquisition in a clustered regularly interspaced short palindromic repeats array. Alternatively, phage resistance was conferred by a prophage originating from an ultravirulent phage with a restored ability to lysogenize. Our results demonstrate that prophages are a potential source of ultravirulent phages that can successfully infect most of the susceptible bacteria. This suggests that prophages can play important roles in the short-term temporal variations observed in the composition of the gut microbiota.

中文翻译：

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来自内部的敌人：Roseburia gutis 的一种噬菌体系统性地在小鼠肠道中裂解，通过 CRISPR 间隔物获得来驱动细菌适应。

尽管人类肠道微生物群在门水平上的整体时间稳定性，但已观察到物种丰度的强烈变化。对于促进或破坏微生物群落稳定性的因素，我们还远未清楚。环境因素，如食物或抗生素的使用，会改变肠道微生物群的组成，但它们的总体影响仍然相对较低。噬菌体是感染细菌的病毒，可能构成解释物种丰度随时间变化的重要因素。肠道细菌含有许多前噬菌体或休眠病毒，它们可以进化成超毒性噬菌体突变体，可能导致重要的细菌死亡。这种现象是否发生在哺乳动物的微生物群中很大程度上尚未得到探索。在这里，我们研究了定殖于肠道罗斯氏菌（人类肠道微生物群的主要共生体）和大肠杆菌（同一微生物群的次优势成员）的温带噬菌体-细菌共同进化。我们表明，肠杆菌 L1-82 含有两种活跃的前噬菌体 Jekyll 和 Shimadzu。我们观察了小鼠体内超毒性 Shimadzu 噬菌体突变体的系统进化，这导致了肠杆菌种群的崩溃。第二步，噬菌体感染推动了宿主噬菌体抗性的快速反进化，主要是通过在聚集的规则间隔短回文重复阵列中获得噬菌体衍生的间隔物。或者，噬菌体抗性由源自具有恢复的溶原化能力的超毒性噬菌体的原噬菌体赋予。我们的研究结果表明，原噬菌体是超强噬菌体的潜在来源，可以成功感染大多数易感细菌。这表明前噬菌体可以在肠道微生物群组成中观察到的短期时间变化中发挥重要作用。