McMaster University and Queen’s University researchers discovered a gut bacterial ‘super-producer’ of histamine that can cause pain flare-ups in some irritable bowel syndrome (IBS) patients. The culprit is Klebsiella aerogenes, also known as the McMaster-Queen (MQ) strain, which has been found in up to 25% of IBS patients’ gut microbiota samples.

What is irritable bowel syndrome?

The disease in which the large intestine is frequently affected is known as irritable bowel syndrome (IBS). Signs and symptoms include diarrhea, cramping, pain in the stomach, gas, bloating, and sometimes diarrhea and constipation both.

The exact cause of IBS is unknown. However, several factors appear to play a role, including

  1. Contractions of the intestine’s muscles: The intestines are lined with layers of muscles that contract as food passes through the digestive tract. Stronger and longer-lasting contractions can cause gas, bloating, and diarrhea. Weak intestinal contractions can impede food transit and result in the formation of stiff, dry stools.
  2. The nervous system: When the abdomen stretches due to gas or stool, abnormalities in the nerves in the digestive system may cause to feel more discomfort than usual. Inadequately coordinated signals between the brain and the intestines can cause the body to overreact to normal digestive process changes, resulting in pain, diarrhea, or constipation.
  3. Severe infection: IBS can develop as a result of a severe bout of diarrhea (gastroenteritis) caused by bacteria or viruses. IBS may also be linked to an overabundance of bacteria in the intestines (bacterial overgrowth).
  4. Stress in childhood: Stressful experiences, particularly when they were young, increase the risk of developing IBS symptoms in a person.
  5. Microbe changes in the gut: Examples include modifications to the bacteria, fungus, and viruses that often live in the intestines and are crucial to good health. The bacteria in persons with IBS may be different from those in healthy individuals, according to studies.

IBS can have a negative impact on one’s quality of life. People with IBS miss three times as many days of work than those without bowel issues, according to studies.

Experiencing IBS symptoms can result in depression or anxiety. Additionally, anxiety and despair might make IBS worse.

Klebsiella aerogenes: The culprit behind flare-up of pains in irritable bowel syndrome patients

What has the new research revealed?

Researchers studied stool microbiota samples from both Canadian and American patient cohorts and discovered a gut bacterial ‘super-producer’ of histamine, which can cause pain flare-ups in some irritable bowel syndrome (IBS) patients. Researchers followed these patients for several months and discovered high levels of stool histamine when they reported severe pain and low levels of stool histamine when they were pain-free.

By studying germ-free mice colonized with gut microbiota from IBS patients, the McMaster-team Queen’s identified the bacterium Klebsiella aerogenes as the primary histamine producer. They discovered that reducing the intake of fermentable carbohydrates reduced abdominal pain in IBS patients, which was accompanied by changes in the gut microbiota and lower urinary histamine concentrations.

They investigated the role of gut bacteria and the neuroactive mediator histamine in visceral hypersensitivity using germ-free mice colonized with fecal microbiota from IBS patients. Visceral hyperalgesia and mast cell activation were observed in germ-free mice colonized with the fecal microbiota of IBS patients with high but not low urinary histamine. When these mice were fed a diet low in fermentable carbohydrates, their visceral hypersensitivity and mast cell accumulation in the colon decreased.

Klebsiella aerogenes: The culprit behind flare-up of pains in irritable bowel syndrome patients

They discovered that the fecal microbiota of patients with IBS who had high urinary histamine but not low urinary histamine produced a lot of histamine in vitro. Klebsiella aerogenes, which carries a histidine decarboxylase gene variant, was identified as a major producer of this histamine. When compared to healthy people, this bacterial strain was abundant in the fecal microbiota of three independent cohorts of IBS patients. In germ-free mice colonized with the high histamine-producing irritable bowel syndrome fecal microbiota, pharmacological blockade of the histamine 4 receptor inhibited visceral hypersensitivity and decreased mast cell accumulation. These findings imply that therapeutic strategies targeting bacterial histamine could aid in the treatment of visceral hyperalgesia in a subset of IBS patients suffering from chronic abdominal pain.