IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, Toulouse, France.
CHU Toulouse, Hôpital Purpan, Service de Bactériologie-Hygiène, Toulouse, France.
mSphere. 2020 Jul 1;5(4):e00589-20. doi: 10.1128/mSphere.00589-20.
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 strain, (ii) a commensal strain plus a genotoxic strain, (iii) a commensal strain plus a nongenotoxic 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 and taxa belonging to the , a modest effect on overall microbial diversity, and no effect on gut microbiome. At day 35, mice that received the genotoxic strain showed lower and taxa belonging to the , 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. Infections of genotoxic spread concomitantly with urbanized progression. These bacteria may prompt cell senescence and affect DNA stability, inducing cancer via the production of colibactin, a genotoxin shown capable of affecting host DNA in eukaryotic cells. In this study, we show that the action of colibactin may also be directed against other bacteria of the gut microbiota in which genotoxic bacteria have been introduced. Indeed, the presence of genotoxic induced a change in both the structure and function of the gut microbiota. Our data indicate that genotoxic may use colibactin to compete for gut niche utilization.
肠道微生物群的常驻细菌产生的遗传毒素 colibactin 可能通过诱导宿主细胞中的 DNA 双链断裂而具有致癌作用。然而，colibactin 对肠道微生物群组成和功能的影响尚不清楚。为了解决这一问题，我们设计了一项实验，即将以下共生菌株定植于怀孕的小鼠体内：（i）共生菌株，（ii）共生菌株加上遗传毒性菌株，（iii）共生菌株加上无法产生成熟 colibactin 的非遗传毒性突变菌株。然后，我们分析了出生后第 15 天和第 35 天的幼崽的肠道微生物群。在第 15 天，出生时用遗传毒性菌株定植的小鼠显示出较低水平的 和属于 的分类群，对整体微生物多样性有适度影响，对肠道微生物群没有影响。在第 35 天，接受遗传毒性菌株的小鼠显示出较低的 和属于 的分类群，同时对整体微生物多样性有强烈影响，与 DNA 修复相关的微生物功能更高。此外，遗传毒性菌株强烈影响了第 15 天至第 35 天接受遗传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，colibactin 不仅针对宿主，还可能对肠道微生物群发挥其遗传毒性作用。遗传毒性 菌株的感染与城市化进程同时发生。这些细菌可能会促使细胞衰老并影响 DNA 稳定性，通过产生 colibactin 诱导癌症，这种遗传毒素被证明能够影响真核细胞中的宿主 DNA。在这项研究中，我们表明 colibactin 的作用也可能针对引入遗传毒性 细菌的肠道微生物群中的其他细菌。事实上，遗传毒性 的存在导致肠道微生物群的结构和功能发生变化。我们的数据表明，遗传毒性 可能利用 colibactin 来争夺肠道生态位的利用。
