The genotoxin colibactin produced by resident bacteria of the gut microbiota may have tumorigenic effect by inducing DNA double-strand breaks in host cells. Yet, the effect of colibactin on gut microbiota composition and functions remains unknown. To address this point, we designed an experiment in which pregnant mice were colonized with the following: (i) a commensal Escherichia coli strain, (ii) a commensal E. coli strain plus a genotoxic E. coli strain, (iii) a commensal E. coli strain plus a nongenotoxic E. coli mutant strain unable to produce mature colibactin. Then, we analyzed the gut microbiota in pups at day 15 and day 35 after birth. At day 15, mice that were colonized at birth with the genotoxic strain showed lower levels of Proteobacteria and taxa belonging to the Proteobacteria, a modest effect on overall microbial diversity, and no effect on gut microbiome. At day 35, mice that received the genotoxic strain showed lower Firmicutes and taxa belonging to the Firmicutes, together with a strong effect on overall microbial diversity and higher microbial functions related to DNA repair. Moreover, the genotoxic strain strongly affected gut microbial diversity evolution of pups receiving the genotoxic strain between day 15 and day 35. Our data show that colibactin, beyond targeting the host, may also exert its genotoxic effect on the gut microbiota.

中文翻译：

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基因毒素 Colibactin 塑造小鼠肠道微生物群。

肠道微生物群中的常驻细菌产生的基因毒素大肠杆菌素可能通过诱导宿主细胞中的 DNA 双链断裂而具有致瘤作用。然而，大肠杆菌素对肠道微生物群组成和功能的影响仍然未知。为了解决这一点，我们设计了一个实验，在该实验中，怀孕的小鼠被以下物质定植：（i）共生大肠杆菌菌株，（ii）共生大肠杆菌菌株加上基因毒性大肠杆菌菌株，（iii）共生大肠杆菌菌株大肠杆菌菌株加上非遗传毒性大肠杆菌不能产生成熟大肠杆菌素的突变菌株。然后，我们分析了幼崽在出生后第 15 天和第 35 天的肠道微生物群。在第15天，出生时与遗传毒性菌株被殖民的小鼠表现出的较低水平变形菌和属于类群变形菌，对整个微生物多样性适度的影响，并在肠道微生物没有影响。在第35天，即接收到的基因毒性菌株的小鼠显示更低的硬壁菌门和门类属于硬壁菌门，以及对整体微生物多样性的强烈影响和与 DNA 修复相关的更高微生物功能。此外，基因毒性菌株在​​第 15 天和第 35 天之间强烈影响接受基因毒性菌株的幼崽的肠道微生物多样性进化。我们的数据表明，大肠杆菌素除了靶向宿主外，还可能对肠道微生物群发挥其基因毒性作用。