Scientists have identified an Achilles heel in a type of gut bacteria that causes intestinal inflammation in patients with Crohn's disease. The new finding may lead to more targeted therapies for the difficult to treat disease, according //to Weill Cornell Medicine and NewYork-Presbyterian investigators.
‘The treatments that precisely target the inflammatory cascade might help reduce inflammation while preserving beneficial bacteria. ’
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In a study published Feb. 3 in Cell Host and Microbe, the investigators showed that patients with Crohn's disease have an overabundance of a type of gut bacteria called adherent-invasive Escherichia coli (AIEC), which promotes inflammation in the intestine. Their experiments revealed that a metabolite produced by the bacteria interacts with immune system cells in the lining of the intestine, triggering inflammation. Interfering with this process, by either reducing the bacteria's food supply or eliminating a key enzyme in the process relieved gut inflammation in a mouse model of Crohn's disease.
"The study reveals a therapeutically targetable weak point in the bacteria," said senior author Dr. Randy Longman, associate professor of medicine in the Division of Gastroenterology and Hepatology and the Director of the Jill Roberts Center for Inflammatory Bowel Disease at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center.
To find this "Achilles heel," Dr. Longman and his colleagues, including Drs. Ellen Scherl and Chun-Jun Guo at Weill Cornell Medicine and collaborators Dr. Gretchen Diehl at Memorial Sloan Kettering and Dr. Kenneth Simpson at Cornell's Ithaca campus, targeted a process the AIEC bacteria uses to convert a byproduct of sugar fermentation in the gut to grow.
Specifically, the AIEC uses 1,2-propanediol, a byproduct of the breakdown of a type of sugar called fucose that is found in the lining of the intestines. When the AIEC converts 1,2-propanediol, it produces propionate, which the study showed interacts with a type of immune system cell called mononuclear phagocytes that are also found in the lining of the gut. This sets off a cascade of inflammation. Next, the investigators genetically engineered AIEC bacteria to lack a key enzyme in this process called propanediol dehydratase. Without propanediol dehydratase, the bacteria do not set off a cascade of inflammation in a mouse model of Crohn's disease. Reducing the available supply of fucose in the animal's gut also reduced inflammation.
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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.
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"From a clinical perspective, that's interesting because it may help us stratify people for whom one intervention or another maybe more useful," Dr. Longman said.
Source-Eurekalert