Finding ‘Achilles heel’ in gut bacteria could lead to targeted treatments for Crohn’s disease

“Achilles heel” may be found in a type of gut bacteria that causes intestinal inflammation in patients with Crohn’s disease to more targeted treatments for the difficult-to-treat disease, according to Weill Cornell Medicine and NewYork- Presbyterian.

In a study published February 3 in Cell Host and Microbe, the researchers showed that patients with Crohn’s disease have an overabundance of a gut bacteria type called Escherichia coli (AIEC) that is aggressive, aggressive, which promotes inflammation in the abdomen. Their tests showed that a metabolite produced by the bacteria interacts with cells of the immune system in the lining of the abdomen, leading to inflammation. By interfering with this process, either reducing the food supply of the bacteria or eliminating a key enzyme in the process relieves gut inflammation in a mouse model of Crohn’s disease.

“The study reveals a therapeutically targeted weak point in the bacteria,” said lead author Dr. Randy Longman, professor of medicine in the Department of Gastroenterology and Hepatology and Director of the Jill Roberts Center for Infectious Infectious Disease at Weill Cornell Medicine and NewYork-Presbyterian / Weill Cornell Medical Center.

To find this “Achilles heel”, Dr. Longman and his colleagues, Drs among them. Ellen Scherl and Chun-Jun Guo at Weill Cornell Medicine and colleagues Dr. Gretchen Diehl at the Sloan Kettering Memorial and Dr. Kenneth Simpson at the Ithaca Cornell campus, focused on a process that AIEC bacteria use to by-product turn sugar fermentation in the skewer to grow.

In particular, the AIEC uses 1,2-propanediol, a byproduct of the breakdown of a type of sugar called fucose found in the lining of the abdomen. When the AIEC alters 1,2-propanediol, it produces propionate, which the study showed interacts with a type of immune system cell called mononuclear phagocytes that is also found in the cleavage line. . This prevents inflammation.

Next, the researchers tested AIEC’s genetic bacteria for the lack of a key enzyme in this process called propanediol dehydratase. Without propanediol dehydratase, the bacteria do not inhibit inflammation in a mouse model of Crohn’s disease. Reducing the supply of fucose available in the gut of the animal also reduced inflammation.

“Alteration of a single metabolic pathway in a single type of bacteria can have a significant impact on intestinal inflammation,” said the study’s co-lead author, Dr. Monica Viladomiu, a postdoctoral fellow in medicine in the Department of Gastroenterology and Hepatology and in the Jill Roberts Institute for Research on Infectious Inflammatory Disease at Weill Cornell Medicine. Maeva Metz, a graduate doctoral candidate at the Weill Cornell School of Medical Sciences in Dr. Longman’s laboratory, is also a lead author.

The discovery could lead to better treatments for Crohn’s disease, a type of inflammatory bowel disease that affects more than 4 million people worldwide. Currently, patients with Crohn’s disease are often treated with antibiotics, which can kill both beneficial and harmful bacteria causing unwanted side effects. But therapies that specifically target the preventive found by Dr. Longman and colleagues could help reduce inflammation while retaining beneficial bacteria.

“If we can develop small molecular-weight drugs that inhibit propanediol dehydratase or use dietary changes to reduce fucose, we may be able to reduce intestinal inflammation in patients with Crohn’s disease with less of effects, “said Dr. Longman, who is also a member of the Jill Roberts Institute for Research on Infectious Inflammatory Disease.

One of the next steps for the team is to test for potential treatments. They also plan to investigate the potential role of an enzyme called fucosyltransferase 2 in protecting the gut against this inhibitory effect. Dr. Longman explained that many patients with Crohn’s disease have mutations in the gene that encodes this enzyme, leaving it inactive.

“From a clinical perspective, that’s interesting because it may help us stratify people who may find one intervention or another more useful,” Dr. Longman said.