The Genotoxin Colibactin Shapes Gut Microbiota in Mice

ABSTRACT 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 exper...

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Autores principales: Sophie Tronnet, Pauline Floch, Laetitia Lucarelli, Deborah Gaillard, Patricia Martin, Matteo Serino, Eric Oswald
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Publicado: American Society for Microbiology 2020
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spelling oai:doaj.org-article:4ad29f59c52b4b4d93e0252aeed255b82021-11-15T15:30:51ZThe Genotoxin Colibactin Shapes Gut Microbiota in Mice10.1128/mSphere.00589-202379-5042https://doaj.org/article/4ad29f59c52b4b4d93e0252aeed255b82020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00589-20https://doaj.org/toc/2379-5042ABSTRACT 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.Sophie TronnetPauline FlochLaetitia LucarelliDeborah GaillardPatricia MartinMatteo SerinoEric OswaldAmerican Society for Microbiologyarticlecolibactinenterobacteriagut microbiota dysbiosismicrobiomeMicrobiologyQR1-502ENmSphere, Vol 5, Iss 4 (2020)
institution DOAJ
collection DOAJ
language EN
topic colibactin
enterobacteria
gut microbiota dysbiosis
microbiome
Microbiology
QR1-502
spellingShingle colibactin
enterobacteria
gut microbiota dysbiosis
microbiome
Microbiology
QR1-502
Sophie Tronnet
Pauline Floch
Laetitia Lucarelli
Deborah Gaillard
Patricia Martin
Matteo Serino
Eric Oswald
The Genotoxin Colibactin Shapes Gut Microbiota in Mice
description ABSTRACT 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.
format article
author Sophie Tronnet
Pauline Floch
Laetitia Lucarelli
Deborah Gaillard
Patricia Martin
Matteo Serino
Eric Oswald
author_facet Sophie Tronnet
Pauline Floch
Laetitia Lucarelli
Deborah Gaillard
Patricia Martin
Matteo Serino
Eric Oswald
author_sort Sophie Tronnet
title The Genotoxin Colibactin Shapes Gut Microbiota in Mice
title_short The Genotoxin Colibactin Shapes Gut Microbiota in Mice
title_full The Genotoxin Colibactin Shapes Gut Microbiota in Mice
title_fullStr The Genotoxin Colibactin Shapes Gut Microbiota in Mice
title_full_unstemmed The Genotoxin Colibactin Shapes Gut Microbiota in Mice
title_sort genotoxin colibactin shapes gut microbiota in mice
publisher American Society for Microbiology
publishDate 2020
url https://doaj.org/article/4ad29f59c52b4b4d93e0252aeed255b8
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