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Abstract
The neonatal gut is rapidly colonized by a newly dominant group of commensal Escherichia coli strains among which a large proportion produces a genotoxin called colibactin. In order to analyze the short- and long-term effects resulting from such evolution, we developed a rat model mimicking the natural transmission of E. coli from mothers to neonates. Genotoxic and non-genotoxic E. coli strains were equally transmitted to the offspring and stably colonized the gut across generations. DNA damage was only detected in neonates colonized with genotoxic E. coli strains. Signs of genotoxic stress such as anaphase bridges, higher occurrence of crypt fission and accelerated renewal of the mature epithelium were detected at adulthood. In addition, we observed alterations of secretory cell populations and gut epithelial barrier. Our findings illustrate how critical is the genotype of E. coli strains acquired at birth for gut homeostasis at adulthood.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
We are grateful to Pr Ulrich Dobrindt for providing the M1/5 E. coli strain and shotgun sequence data (Münster University, Germany). The authors wish to thank the staff at the animal service facility of Toxalim for animal care. We also thank members of the Joost Van Meerwijk lab (Centre de Physiopathologie de Toulouse-Purpan, CPTP) for obtaining irradiated rats, the staff of the histopathology platform of UMS US 006 and imagery platform of CPTP for excellent technical help. This work was supported by grants from the French National Research Agency (ANR-09-MIEN-005–01) and the Association pour la Recherche sur le Cancer (ARC DOC20110602919).