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Functional screening of human gut microbiota reveals a family of small molecule genotoxins called indolimines in patients with inflammatory bowel disease (IBD), according to a new study. According to the findings, these genotoxic metabolites may play a role in the development of colorectal cancer (CRC) – the second leading cause of cancer deaths worldwide.

Individuals with IBD are at increased risk of developing CRC. Previous research shows that microbiota-derived genotoxic metabolites, which damage or mutate DNA, likely play a critical role in driving CRC pathogenesis. However, can u get high off celebrex 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 evaluate the genotoxicity of a large collection of indigenous microbiota from patients with IBD. Cao et al. report the discovery of a previously unknown family of DNA-damaging genotoxic microbial metabolites they term the indolimines, which are produced by the CRC-associated gut microbe Morganella morganii. The authors demonstrate that, in a mouse model of colon cancer, M. morganii exacerbated tumor growth. However, a non-indolimine-producing mutant strain lacked this observed genotoxicity and did not influence tumorigenesis.

According to Cao et al., the findings underscore the diverse impacts that small-molecule metabolites from the microbiome have on host biology and disease. "The study of Cao et al. reveals that the human colon microbiota – already highly implicated in CRC pathogenesis – has a broad-ranging, previously unimagined capacity to produce genotoxins with colon disease-inducing potential," write Jens Puschhof and Cynthia Sears in a related Perspective.

Source:

American Association for the Advancement of Science (AAAS)

Journal reference:

Cao, Y., et al. (2022) Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites. Science. doi.org/10.1126/science.abm3233.

Posted in: Medical Science News | Medical Condition News

Tags: Cancer, Chemicals, Colon Cancer, Colorectal, Colorectal Cancer, DNA, Inflammatory Bowel Disease, Metabolites, Microbiome, Molecule, Mouse Model, OCT, Research, Tumor, Tumorigenesis

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