Study Identifies Receptor for Gut Bacterium Toxin Linked to Colon Tumors

A study published in Nature has identified the receptor that allows a toxin produced by certain strains of the gut bacterium Bacteroides fragilis to bind to colon cells and initiate damage linked to tumor formation. The paper, titled 'A pro-carcinogenic bacterial toxin binds claudin-4 to cleave E-cadherin,' appears in volume 654, pages 504–512.

Researchers led by Johns Hopkins Medicine used a genome-wide CRISPR screening approach to determine that the toxin, known as BFT, attaches to the claudin-4 protein.

Removing claudin-4 from colon cells prevented the toxin from binding and starting the damage process. Bacteroides fragilis is present in up to 20 percent of healthy people. Scientists have known for more than 15 years that only enterotoxigenic strains, which produce BFT, contribute to colon tumor formation.

The toxin damages E-cadherin, a protein that maintains the colon's protective barrier, leading to chronic inflammation. In animal studies, a molecular decoy designed to mimic the claudin-4 receptor intercepted the toxin and prevented tissue damage. Rosario Ligresti, chief of the Gastroenterology Division at Hackensack University Medical Center, said the findings strengthen evidence of a direct biological pathway from bacterial toxin to colon lining damage and increased cancer risk.

Cynthia Sears, senior author and Bloomberg–Kimmel Professor of Cancer Immunotherapy at Johns Hopkins, stated that it remains too early to know whether blocking the toxin will prevent colon cancer in people. She said the next steps would require complex studies with clear endpoints to assess efficacy in blocking or attenuating the risk of progressive colon polyps or colon cancer.