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Commensal gut microbes from IBD patients produce genotoxic metabolites
Functional screening of the human gut microbiota reveals a family of small molecule genotoxins called indolimins in patients with inflammatory bowel disease (IBD), according to a new study. According to the results, these genotoxic metabolites may play a role in the development of colorectal cancer (CRC), the second leading cause of cancer death worldwide. Individuals with IBD are at increased risk of developing CRC. Previous research indicates that microbiota-derived genotoxic metabolites that damage or mutate DNA likely play a critical role in the development of CRC pathogenesis. However, the full spectrum of genotoxic chemicals produced by commensal gut microbes remains poorly defined. To make this…
Commensal gut microbes from IBD patients produce genotoxic metabolites
Functional screening of the human gut microbiota reveals a family of small molecule genotoxins called indolimins in patients with inflammatory bowel disease (IBD), according to a new study. According to the results, these genotoxic metabolites may play a role in the development of colorectal cancer (CRC), the second leading cause of cancer death worldwide.
Individuals with IBD are at increased risk of developing CRC. Previous research indicates that microbiota-derived genotoxic metabolites that damage or mutate DNA likely play a critical role in the development of CRC pathogenesis. However, the full spectrum of genotoxic chemicals produced by commensal gut microbes remains poorly defined.
To better understand these molecules, Yiyun Cao and colleagues developed a functional screen to systematically assess the genotoxicity of a large collection of native microbiota from patients with IBD. Cao et al. report the discovery of a previously unknown family of DNA-damaging genotoxic microbial metabolites, which they term indolimines, produced by the CRC-associated gut microbe Morganella morganii. The authors show that M. morganii exacerbated tumor growth in a mouse model of colon cancer. However, a non-indolimine-producing mutant strain lacked this observed genotoxicity and did not affect tumorigenesis.
According to Cao et al. The results highlight the diverse effects that small molecule metabolites from the microbiome have on host biology and disease. "The study by Cao et al. shows that the human colon microbiota – already heavily implicated in CRC pathogenesis – has a widespread, previously unsuspected ability to produce genotoxins with intestinal disease-causing potential," write Jens Puschhof and Cynthia Sears in a related Perspective.
Source:
American Association for the Advancement of Science (AAAS)
Reference:
Cao, Y., et al. (2022) Commensal microbiota of patients with inflammatory bowel disease produce genotoxic metabolites. Science. doi.org/10.1126/science.abm3233.
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