Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites

Area of Science:

• Microbiology
• Genetics
• Oncology

Background:

• Microbiota-derived metabolites can cause DNA damage, contributing to colorectal cancer (CRC).
• The complete range of genotoxic chemicals produced by gut microbes is not fully understood.
• Inflammatory bowel disease (IBD) patients harbor gut microbes that may produce genotoxins.

Purpose of the Study:

• To systematically evaluate the genotoxicity of gut commensal bacteria.
• To identify novel genotoxic metabolites produced by the gut microbiome.
• To investigate the role of specific genotoxins in colorectal cancer development.

Main Methods:

• Developed a pipeline to screen gut commensal isolates for genotoxicity.
• Collected and analyzed gut microbes from IBD patients.
• Utilized bacterial genetics to create mutants and assess genotoxin production.
• Assessed the impact of microbial genotoxins on colon tumorigenesis in mouse models.

Main Results:

• Identified gut microbes from diverse phylogenetic groups producing genotoxic metabolites.
• Discovered a new family of genotoxins, termed indolimines, produced by *Morganella morganii*.
• A *M. morganii* mutant unable to produce indolimines showed no genotoxicity and did not worsen colon tumors in mice.

Conclusions:

• The gut microbiome harbors a previously unrecognized array of genotoxic small molecules.
• Indolimines produced by *Morganella morganii* are a novel class of genotoxins contributing to CRC.
• These findings highlight the potential impact of microbial genotoxins on host health and disease.