Irritable bowel syndrome caused by histamine-producing gut bacteria
By producing histamine, certain intestinal bacteria can lead to chronic abdominal pain and irritable bowel syndrome. Diets with reduced fermentable carbohydrates and drugs directed against bacterial histamine could serve as therapy here.
A research team from McMaster University and Queen's University has discovered the bacterial "histamine superproducer" in the gut that can lead to chronic abdominal pain and irritable bowel syndrome. The results of the corresponding study were published in the journal Science Translational Medicine.
Intestinal flora affects health
Gut flora is associated with far-reaching health effects, extending far beyond the digestive tract. Recent studies have shown, for example, that the gut flora influences the development of rheumatic diseases and influences the brain and behavior via the gut-brain axis.
In the digestive tract, however, the health effects of the gut microbiota are particularly evident. Gut flora has previously been associated with chronic abdominal pain and irritable bowel syndrome, but the specific pathophysiological mechanisms remain unclear.
Search for physiopathological mechanisms
In the current study, the researchers attempt to decipher this. To do this, they first examined stool samples from Canadian and American patient cohorts.
“We followed these patients for several months and found high histamine levels in the stool when the patients reported severe pain and low histamine levels when they had no pain,” the study said. lead author of the study, Professor Premysl Bercik of McMaster University.
Klebsiella aerogenes major histamine producer
In experiments on mice, the research team was then able to identify the bacterium Klebsiella aerogenes as the most important producer of histamine. According to the researchers, the bacteria can convert dietary histidine, an essential amino acid found in animal and vegetable proteins, into histamine.
According to the researchers, the bacterial strain was also very frequently represented in the fecal microbiota of three independent cohorts of patients with irritable bowel syndrome compared to healthy people.
The experiments also clearly showed that bacterial histamine activates the gut's immune system via the histamine-4 receptor, which attracts immunological mast cells to the gut. Mast cells produce even more histamine and other pain mediators, causing inflammation and pain, the team explains.
Diet with fewer fermentable carbohydrates
If the mice were fed a diet containing fewer fermentable carbohydrates, a reduction in so-called visceral hypersensitivity and the accumulation of mast cells in the large intestine were detectable.
Reducing fermentable carbohydrate intake also improved abdominal pain in patients with irritable bowel syndrome, which was associated with changes in gut flora and lower urine histamine concentrations.
New therapeutic options
In mouse studies, pharmacological blockade of the histamine-4 receptor also inhibited so-called visceral hypersensitivity and reduced mast cell accumulation in the large intestine.
This suggests that therapeutic strategies targeting bacterial histamine could help treat many people with irritable bowel syndrome and chronic abdominal pain.
"Now that we know how histamine is produced in the gut, we can identify and develop therapies that target histamine-producing bacteria," said lead author Giada de Palma from McMaster University.
"Although the treatment of mast cells in irritable bowel syndrome has been explored, a new approach based on our research would be to target the bacterial production of histamine or the H4R pathway", adds Professor Bercik.
Co-author Professor Stephen Vanner of Queen's University also hopes that blocking H4 receptors could prevent the recruitment of mast cells to the large intestine and therefore the development of abdominal pain. (fp)
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Sources:Giada De Palma, Chiko Shimbori, David E. Reed, Yang Yu, Virginia Rabbia, Jun Lu, Nestor Jimenez-Vargas, Jessica Sessenwein, Cintya Lopez-Lopez, Premysl Bercik et al: Histamine production by the gut microbiota induces a visceral hyperalgesia by histamine 4 receptor signaling in mice; in Science Translational Medicine (published 2022-07-27), science.org McMaster University: Histamine-producing gut bacteria may trigger chronic abdominal pain (published 2022-07-27), eurekalert.org
This article contains general advice only and should not be used for self-diagnosis or treatment. It cannot substitute a visit to the doctor.