Colonization with Murine pks+ Escherichia coli under Non-Inflammatory Conditions

Area of Science:

• Microbiology
• Gastroenterology
• Oncology

Background:

• pks+ Escherichia coli strains produce colibactin, a genotoxin linked to colorectal cancer (CRC) development.
• Early-onset CRC is rising, particularly in younger populations, with pks+ E. coli implicated as a key factor.
• Colibactin causes DNA damage and mutations in pathways critical for cell proliferation and differentiation, driving CRC.

Purpose of the Study:

• To detail a reproducible method for establishing pks+ E. coli colonization in mice under non-inflammatory conditions.
• To investigate the effect of dietary fiber, specifically inulin, on pks+ E. coli colonization and growth in a murine model.
• To provide a valuable tool for studying preventative and therapeutic strategies against CRC linked to pks+ E. coli.

Main Methods:

• Oral gavage of antibiotic-conditioned C57BL/6 mice with the pks+ E. coli strain NC101.
• Assessment of colonization through quantification of lactose-fermenting gram-negative colony-forming units (CFUs) and quantitative PCR in stool samples.
• Analysis of the Enterobacteriaceae family abundance and clbP gene levels to confirm bacterial presence and activity.

Main Results:

• Successful colonization of mice with E. coli NC101 was achieved and validated.
• Supplementation with the dietary fiber inulin significantly promoted pks+ E. coli growth.
• Inulin supplementation led to increased CFU recovery, higher Enterobacteriaceae abundance, and elevated clbP gene levels.

Conclusions:

• The developed mouse model provides a robust platform for studying pks+ E. coli colonization and its role in CRC.
• Dietary inulin can enhance the growth of this CRC-associated pathobiont, suggesting potential dietary interactions in CRC development.
• This model facilitates research into targeted interventions for CRC prevention and treatment, focusing on the pathobiont E. coli.