Scientists finally discover how a common gut bacterium can trigger colon cancer — SkimNews
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- Bacteroides fragilis is found in the intestines of up to 20% of healthy people, and certain strains produce BFT, a toxin that damages the colon’s protective lining, causes chronic inflammation and promotes tumor formation; a 2009 Nature Medicine study demonstrated the tumor link.
- Claudin-4 emerged from a genome-wide CRISPR screen led by Maxwell White with Matthew Waldor’s Harvard Medical School lab as the essential receptor for BFT; disabling its gene stopped the toxin from binding to colon cells and attacking E-cadherin.
- BFT formed a tightly bound one-to-one complex with claudin-4 in laboratory experiments with the Molecular Biology Institute of Barcelona, providing direct physical evidence for the previously missing toxin-receptor interaction.
- Johns Hopkins Kimmel Cancer Center researchers developed a soluble claudin-4-sequence decoy that intercepted BFT before it bound colon cells, and the construct protected mice from BFT-induced damage in work with Min Dong’s Harvard Medical School lab.
- Nature paper notes key limits: the exact 3D structure of the BFT–claudin-4 complex remains uncaptured, AlphaFold could not fully resolve it, and mouse protection from toxin damage did not establish that the decoy prevents colorectal cancer.
Why it matters: Johns Hopkins researchers have converted a nearly 20-year mechanistic puzzle into a defined intervention point: the 1:1 BFT–claudin-4 docking interaction. In mice, blocking that first attachment prevented toxin-driven tissue damage; Bacteroides fragilis is found in up to 20% of healthy people, but the work did not establish cancer prevention in humans.
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