Local immune response to food antigens drives meal-induced abdominal pain

Nature. 2021 Feb;590(7844):151-156. doi: 10.1038/s41586-020-03118-2. Epub 2021 Jan 13.

Abstract

Up to 20% of people worldwide develop gastrointestinal symptoms following a meal1, leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine. Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H1-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Pain / etiology
  • Abdominal Pain / immunology*
  • Abdominal Pain / microbiology
  • Abdominal Pain / pathology*
  • Adult
  • Allergens / immunology*
  • Animals
  • Citrobacter rodentium / immunology
  • Diarrhea / immunology
  • Diarrhea / microbiology
  • Diarrhea / pathology
  • Enterobacteriaceae Infections / complications
  • Enterobacteriaceae Infections / immunology
  • Enterobacteriaceae Infections / microbiology
  • Female
  • Food / adverse effects*
  • Food Hypersensitivity / complications
  • Food Hypersensitivity / immunology*
  • Food Hypersensitivity / microbiology
  • Food Hypersensitivity / pathology
  • Glutens / immunology
  • Humans
  • Immunoglobulin E / immunology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Intestines / immunology*
  • Intestines / microbiology
  • Intestines / pathology
  • Irritable Bowel Syndrome / etiology
  • Irritable Bowel Syndrome / immunology*
  • Irritable Bowel Syndrome / microbiology
  • Irritable Bowel Syndrome / pathology
  • Male
  • Mast Cells / immunology
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Milk / immunology
  • Ovalbumin / immunology
  • Quality of Life
  • Receptors, Histamine H1 / metabolism
  • Soybean Proteins / immunology
  • Triticum / immunology

Substances

  • Allergens
  • Receptors, Histamine H1
  • Soybean Proteins
  • Immunoglobulin E
  • Glutens
  • Ovalbumin