Histamine from gut bacteria causes pain in irritable bowel

Suddenly doubled over from the stomach pain, trying to reach a toilet as quickly as possible – for people with irritable bowel syndrome it is the order of the day. Their gut reacts with severe pain and diarrhea to certain foods or stress. A new study points to a certain gut bacteria as the main culprit in some of the patients.

It’s about the type of bacteria Klebsiella aerogenes, which profusely populates the gut of some people with the syndrome. The bacteria make large amounts of histamine. This substance worsens the sensitivity to painful stimuli in the intestines. The comprehensive study in mice and patientsthat Wednesday evening in Science Translational Medicine appeared for the first time clearly describes how the microorganisms in the gut – collectively called the microbiome – influence the abdominal pain associated with the syndrome.

“We’ve all been waiting for this study,” says Guy Boeckxstaens, a gastroenterologist and professor of gastroenterology at the Catholic University of Leuven in Belgium, who was not involved in the study. “The microbiome is linked to all kinds of diseases, but it always remains vague. This study really describes the mechanism that contributes to abnormal pain signals in the gut in a subpopulation of patients.”

In people with irritable bowel syndrome (IBS), the bowel makes too many or too few movements, causing diarrhea or constipation, and abdominal pain. Flatulence, abdominal distention and fatigue are also common. The nerves in the intestinal wall are often extra sensitive. The condition affects an estimated 1 in 10 Dutch people.

Vegetables, fruits, grains and dairy

The researchers previously showed that the severe abdominal pain of patients with IBS is reduced if they eat as few indigestible carbohydrates as possible, which are found in certain vegetables, fruits, grains and dairy – known by the abbreviation fodmap. “People cannot digest these sugar chains,” explains Boeckxstaens. “They attract water in the small intestine and are fermented by bacteria in the large intestine, producing gas, which stretches the colon. Usually you don’t feel any pain, but people with an abnormal pain perception get cramps and pain.”

The relief of abdominal pain with a diet without indigestible sugars was accompanied by changes in the composition of the intestinal flora and a reduction in the amount of histamine in the urine. Histamine is a substance produced by the body, but it is also found in some foods. It is made by the body during an allergic reaction, among other things.

The researchers noticed that in a third of their patients the concentration of histamine in their urine was initially very high. They wanted to know more about that.

For the new study, the gut inhabitants of two groups of patients moved to mice that were born with bacteria-free guts: patients with a high concentration of histamine in their urine, or with a low one. A third group of mice received the gut bacteria from healthy individuals. The animals were fed food with a lot of indigestible carbohydrates.

Mice Abdominal Muscles

After just three weeks, the nerves in the mouse intestines in the high-histamine group were more sensitive to stimuli than those in mice in the low-histamine group or in the control group. The abdominal muscles of the mice in the first group also reacted more vigorously when their colons were stretched.

The histamine turned out to be made by a certain gut bacteria. Klebsiella aerogenes made a hundred times more histamine than other bacteria and was the most common type of bacteria in patients with a lot of histamine in the urine. With a diet low in indigestible sugars, they increased the amount Klebsiella aerogenes of.

The authors also showed that the bacteria’s histamine activates certain immune cells in the colon: mast cells. They then make even more histamine, which increases the sensitivity to pain.

It turned out that histamine from mast cells themselves plays an important role in the disturbed pain perception in people with IBS. from research last year van Boeckxstaens in Nature . “Mass cells in the intestinal wall can be activated by various stimuli – by certain nutrients against which a person has developed a local allergic reaction, or by stress,” he says. “This new study shows that histamine, which is produced by gut bacteria, can also do this.”

Lactic acid-producing bacilli

The researchers also found leads for the treatment of PDS. The histamine production of Klebsiella aerogenes was highest at neutral acidity and decreased sharply when acidity increased. The intestine is usually slightly acidic, mainly due to lactic acid. When lactic acid-producing lactobacilli were co-cultured with Klebsiella, they inhibited histamine production. “The use of probiotics with lactobacilli could help this subgroup of patients, who are carriers of the Klebsiella bacteria,” Boeckxstaens thinks. “That is already being done, but it has not yet been clarified exactly how these probiotics work.”

A strict diet without indigestible carbohydrates is also one way. But that is difficult to maintain, and over time people miss important nutrients. Boeckxstaens: “I advise patients to keep a light form of this diet, and to avoid onions, garlic, legumes and cabbage to prevent gas formation.”

A third possibility is anti-allergic drugs, antihistamines. “We have shown that you can treat PDS patients with medicines against hay fever and are now investigating this in a large study,” says Boeckxstaens. “It is not yet a common treatment, but I notice every day that some general practitioners here in Flanders are already prescribing it to patients.” He advises against it. “Patients are better off doing that as part of a scientific study.”

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