The Genotoxin Colibactin Shapes Gut Microbiota in Mice
Résumé
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. IMPORTANCE Infections of genotoxic Escherichia coli 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 E. coli bacteria have been introduced. Indeed, the presence of
genotoxic E. coli induced a change in both the structure and function of the gut microbiota.
Our data indicate that genotoxic E. coli may use colibactin to compete for
gut niche utilization.
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