Researchers have identified a biological mechanism that explains why some individuals experience abdominal pain when eating certain foods, paving the way for more efficient treatment of IBS.
Through oral tolerance, the mucosal immune system provides a balanced response to pathogens and harmless commensal bacteria or food antigens. This limits unnecessary inflammation and tissue damage. However, viral and bacterial infections can interfere with tolerance to dietary antigens. Infectious gastroenteritis is a significant risk factor for the development of irritable bowel syndrome (IBS). Experts define IBS by a constellation of abdominal pain and altered bowel patterns. Between 3 and 36% of enteric infections lead to new-onset IBS. Additionally, up to 20% of people worldwide develop gastrointestinal symptoms following a meal. Aberrant pain signalling or visceral hypersensitivity (VHS) is a hallmark symptom of IBS.
Immune response to food antigens
In this study, published in Nature, researchers hypothesised that a breakdown of oral tolerance to food antigens caused by a bacterial infection underlies food-induced VHS. Specifically, the team infected mice with Citrobacter rodentium while exposing them to ovalbumin (OVA) in drinking water. OVA is a protein in egg whites, which researchers commonly use in experiments as a model food antigen.
Once the infection was cleared, the team exposed mice to OVA again to see if their immune systems had become sensitised to it. They found that OVA on its own was able to provoke mast cell activation, histamine release and digestive tolerance with increased abdominal pain. This was not reported in mice that had received OVA and were not infected with the bacteria. Interestingly, the team also found that the immune response only occurred in the part of the intestine infected by the bacteria and did not produce more general symptoms of a food allergy.
The researchers then explored whether people with IBS reacted in the same way. They injected food antigens associated with IBS (gluten, wheat, soy and cow milk) into the intestine wall of 12 IBS patients. They found that these individuals produced localised immune reactions similar to that seen in the mice. Most importantly, they observed no reaction in healthy volunteers.
These findings provide a peripheral mechanism that underlies food-induced abdominal pain. Consequently, this creates new possibilities for the treatment of IBS and other related abdominal pain disorders.
Professor Guy Boeckxstaens, lead author, stated:
“Knowing the mechanism that leads to mast cell activation is crucial and will lead to novel therapies for these patients.
Mast cells release many more compounds and mediators than just histamine, so if you can block the activation of these cells, I believe you will have a much more efficient therapy.”
Image credit: By Natalia Gdovskaia – canva.com