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Gut-bacterial toxin linked to colon tumors reportedly binds claudin-4 before damaging colon cells

A soluble claudin-4 decoy protected mice from toxin-induced damage, but the mouse experiments did not establish colorectal cancer prevention.

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Certain strains of Bacteroides fragilis produce BFT, a toxin linked to colon tumor formation. In the reported experiments, BFT attached to claudin-4 before attacking E-cadherin, which helps keep colon cells together. Disabling claudin-4 stopped that attack in colon cells, and a soluble decoy protected mice from toxin-induced damage. Those mouse tests did not show that the approach prevents colorectal cancer, and its safety and effectiveness in people still need study.

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A Johns Hopkins-led team identified claudin-4 as the protein a gut-bacterial toxin called BFT binds before damaging colon cells, according to Johns Hopkins Medicine material published by ScienceDaily. The findings were published in Nature. BFT is made by certain strains of Bacteroides fragilis, a bacterium that can also live in healthy intestines. Its presence alone does not mean a person will develop cancer.

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The toxin attacks E-cadherin, a protein that helps neighboring cells hold together and maintain the colon’s protective barrier. Researchers had known BFT damaged E-cadherin but had not pinned down how it attached to cells first. In a genome-wide CRISPR screen of colon-lining cells, the team switched off genes to find which ones BFT needed to bind and cause damage. The researchers report that when they disabled the gene for claudin-4, BFT could no longer bind the cells or attack E-cadherin. They also report that laboratory experiments found BFT and claudin-4 bound tightly, with each toxin molecule pairing with one receptor molecule.

The team made a soluble protein carrying claudin-4 sequences to draw BFT away from colon cells. In mouse experiments, the team reports that the decoy intercepted the toxin and protected against BFT-induced damage. The mouse experiments did not establish that the decoy prevents colorectal cancer. The Johns Hopkins Medicine account says further experiments are needed to determine whether it can safely and effectively prevent toxin-related disease in people.

Gut-bacterial toxin linked to colon tumors reportedly binds claudin-4 before damaging colon cells

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