The Genotoxin Colibactin Shapes Gut Microbiota in Mice

Area of Science:

• Microbiology
• Gut Microbiome Research
• Genotoxicology

Background:

• Colibactin, a genotoxin from Escherichia coli, can induce DNA damage in host cells and is linked to cancer.
• The impact of colibactin on the gut microbiota composition and functions has not been previously understood.
• Genotoxic E. coli infections are increasing with urbanization, highlighting the need to study their broader effects.

Purpose of the Study:

• To investigate the effects of a genotoxic E. coli strain producing colibactin on the gut microbiota of mice.
• To analyze changes in microbial diversity, composition, and function following exposure to colibactin.

Main Methods:

• Pregnant mice were colonized with either a commensal E. coli strain, or a combination of commensal E. coli with a genotoxic or non-genotoxic E. coli strain.
• Gut microbiota in pups were analyzed at 15 and 35 days after birth.
• Microbial diversity, composition (Proteobacteria, Firmicutes), and functional pathways (DNA repair) were assessed.

Main Results:

• At day 15, genotoxic E. coli colonization led to reduced Proteobacteria levels and modest changes in microbial diversity.
• By day 35, genotoxic E. coli significantly reduced Firmicutes, altered overall microbial diversity, and increased DNA repair functions.
• The genotoxic strain markedly influenced the evolution of gut microbial diversity between day 15 and day 35.

Conclusions:

• Colibactin, beyond its effects on host cells, exerts genotoxic effects on the gut microbiota itself.
• Genotoxic E. coli significantly alters the structure and function of the gut microbial community.
• Colibactin may be a mechanism used by genotoxic E. coli to compete for niche utilization within the gut.