‘Achilles’ heel’ of bacteria linked to Crohn’s disease discovered by scientists

NEW YORK — In the last 10 years, research on the human microbiome – the bacterial communities living in and on the human body – has suggested bacteria could play a role in Crohn’s disease. Now, researchers from Weill Cornell Medicine and New York-Presbyterian have discovered a weakness in one of the bacterial species linked to condition.

The species, a type of E. coli, makes a molecule that interferes with immune cells in our intestinal walls and causes inflammation. By preventing production of that molecule or by starving bacteria, that inflammation can be prevented.

Crohn’s disease is a chronic inflammatory bowel condition that causes abdominal pain, diarrhea, weight loss, and fatigue. The disease affects about three million Americans. Often, patients are treated with antibiotics, which can kill beneficial bacteria in the gut and cause unpleasant side effects.

Senior study author Dr. Randy Longman, associate professor of medicine in the Division of Gastroenterology and Hepatology, says he and his colleagues have uncovered a “therapeutically targetable weak point” in this specific bacteria. In other words, they found its Achilles’ heel.

“Changing one metabolic pathway in one type of bacteria can have a big impact on intestinal inflammation,” explains the study’s co-lead author Dr. Monica Viladomiu in a media release.

Throwing a wrench in bacterial metabolism

Researchers used a mouse model of Crohn’s to find a weakness in adherent-invasive Escherichia coli (AIEC). While most people have E. coli in their digestive tracts, this specific species promotes inflammation in the intestine. Gut bacteria breaks down a type of sugar called fucose (common in seaweed, mushrooms, and seeds) into the molecule 1,2-propanediol. AIEC turns 1,2-propanediol into another molecule called propionate. Propionate then interacts with immune cells in the intestinal lining, triggering inflammation.

The researchers created mutant AIEC that couldn’t turn 1,2-propanediol into propionate. They then treated mice with normal AIEC or mutant AIEC and measured intestinal inflammation. The mice with mutant AIEC stayed healthy, but those with normal AIEC had inflamed intestines. The researchers also discovered that simply removing fucose from a mouse’s diet can eliminate gut inflammation.

The study authors say their research suggests that scientists can create treatments for Crohn’s disease that target bad bacteria while preserving good bacteria.

“If we can develop small molecule drugs that inhibit propanediol dehydratase or use dietary modifications to reduce the availability of fucose, we may be able to reduce intestinal inflammation in patients with Crohn’s disease with fewer side effects,” Dr. Longman says.

These findings are published in Cell Host and Microbe.

Leave a Reply

Your email address will not be published. Required fields are marked *