Science: Gut-derived genotoxic metabolites have been linked to cancer

According to a new study, functional screening of the human gut microbiota has revealed the presence of a family
of small molecule genotoxins called indolamine in patients with inflammatory bowel disease (IBD).
According to the findings, these genotoxic metabolites may play a role
in the development of colorectal cancer, the second leading cause of cancer death worldwide.

People with IBD are at increased
risk of CRC.
Previous research has suggested that microbiome-derived genotoxic metabolites, which damage or mutate DNA, may play a key role
in driving the pathogenesis of CRC.
However, the full spectrum of genotoxic chemicals produced by commensal gut microbes remains unclear
.

To better understand these molecules, Yiyun Cao and colleagues developed a functional screening to systematically assess the genotoxicity
of large numbers of local microbiota in IBD patients.
Cao et al.
report a previously unknown family of DNA-damaging genotoxic microbial metabolites, which they call indolemine, which is produced
by the CRC-associated gut microorganism Morganella.
The authors demonstrated that in a mouse model of colon cancer, Mycobacterium Morgani exacerbated tumor growth
.

However, a mutant strain that does not produce indolamine lacks this observed genotoxicity and does not affect tumorigenesis
.
Cao et al.
argue that these findings highlight the different effects
of small molecule metabolites from the microbiome on host biology and disease.

Jens Puschhof and Cynthia Sears write in a related opinion: "The study by Cao et al.
reveals that the human colonic microbiome—already highly correlated with the pathogenesis of colorectal cancer—has a widespread, previously unimaginable ability to
produce colon-inducing genotoxins.
"