Newly discovered gut bacteria overproduces histamine, triggering stomach pain in IBS patients

Researchers from McMaster University and Queen’s University have discovered the culprit that overproduces histamine, resulting in painful inflammation in irritable bowel syndrome (IBS) patients. The bacterial strain responsible, called Klebsiella aerogenes, was found in 25% of gut bacteria samples from this population , including patients from Canada and the United States.

To conduct this study, the team studied germ-free mice that were manipulated to possess the gut environment of an IBS patient. As a control, they did the same thing but with used gut microbes from healthy individuals. Their experiments found that Klebsiella aerogenes converts dietary histidine, an essential protein found in plants and animals, into histamine, which is a well-studied chemical related to pain and sensitivity.

Histamine was then found to activate the immune system in the gut through the histamine-4 receptor, luring immune cells into the intestines. These activated cells end up producing even more histamine, which triggers inflammation and pain. “Now that we know how the histamine is produced in the gut, we can identify and develop therapies that target the histamine producing bacteria,” says first author Giada de Palma, assistant professor of medicine at McMaster, in a statement.

Interestingly, their findings also supported the importance of diet in histamine conversion. Mice with histamine producing bacteria that were fed a low-fermentable carbohydrate diet also saw significantly lowered amounts of histamine produced. The fermentation inhibited the enzyme responsible for histamine generation. The authors believe that this specific finding supports the previously observed discovery that a low fermentable diet supports IBS patients experiencing painful effects of the condition.

“We followed up these patients for several months and found high levels of stool histamine at the time when the patients reported severe pain, and low stool histamine when they were pain-free,” says senior author Premysl Bercik, a gastroenterologist and professor of medicine of McMaster’s Michael G. DeGroote School of Medicine.

Also widely known among researchers is that those with IBS often have more immune cells in their intestinal lining, so some find treatment to be beneficial when it goes after these cells or the histamines, like mast cell stabilizers or antihistamine medication. To take it one step further, this research suggests getting even more target-specific. “Although mast cell treatment in IBS has been explored, a novel approach based on our research would be targeting the bacterial histamine production or H4R pathways,” says Bercik.

While this has the potential to be a breakthrough in treating abdominal pain related to IBS, not every patient will experience this pain for the same reasons. As such, this form of treatment may only work for some. To help identify what works best for a patient, the team believes that more research for identifying biomarkers could help find out what type of medication would work best in response to their pain trigger.

This study is published in the journal Science Translational Medicine.

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