Amylase-Trypsin Inhibitors in Wheat and Other Cereals as Potential Activators of the Effects of Nonceliac Gluten Sensitivity

J Med Food. 2018 Mar;21(3):207-214. doi: 10.1089/jmf.2017.0018. Epub 2018 Jan 9.


Nonceliac gluten sensitivity (NCGS) is a gluten-related gastrointestinal disorder distinct from celiac disease (CD) and gluten allergy that is not easy to diagnose due to the lack of biomarkers. It is characterized by intestinal symptoms and extraintestinal manifestations with the consumption of gluten-containing foods. In contrast to CD, NCGS patients do not present a genetic predisposition or intestinal villi atrophy. Recent studies question the proinflammatory triggering activity of α-gliadin fraction contained in wheat, since it has been demonstrated that the amylase-trypsin inhibitors (ATIs) exert a strong activating effect on the innate immune response. We aimed to analyze the role of ATIs in the activation of innate immunity and in the development of the symptoms characteristic of NCGS. A systematic literature search was made using databases such as MEDLINE, SciELO, Science Direct, and Scopus, with focus on key words such as "amylase-trypsin inhibitors," "wheat," "gluten," and "celiac." Many studies are available on the structure, inhibition mechanism, and immune system effects of ATIs, mainly focused on IgE-mediated reactions. Recently, with the increase of NCGS interest, has increased the literature on the capacity of ATIs contained in wheat to activate the innate immune system. Literature published to date questions the relationship between activation of the innate immune system and gluten in NCGS. ATIs may have acted as interfering contaminant of gluten and appear as potential activator of innate immunity in NCGS patients. In view of their potential impact, more interventional studies are needed to demonstrate the proinflammatory effect of ATIs.

Keywords: gluten; gluten sensitivity; immunity innate; wheat; α-amylase–trypsin inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Edible Grain / adverse effects*
  • Edible Grain / chemistry
  • Enzyme Inhibitors / adverse effects*
  • Enzyme Inhibitors / analysis
  • Enzyme Inhibitors / metabolism
  • Food Intolerance / etiology*
  • Food Intolerance / immunology
  • Food Intolerance / metabolism
  • Food Intolerance / physiopathology
  • Glutens / adverse effects*
  • Glutens / metabolism
  • Hordeum / adverse effects
  • Hordeum / chemistry
  • Humans
  • Immunity, Innate
  • Immunity, Mucosal
  • Intestinal Mucosa / enzymology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Plant Proteins / adverse effects*
  • Plant Proteins / analysis
  • Plant Proteins / metabolism
  • Secale / adverse effects
  • Secale / chemistry
  • Toll-Like Receptors / agonists
  • Toll-Like Receptors / metabolism
  • Triticum / adverse effects
  • Triticum / chemistry
  • Trypsin Inhibitors / adverse effects*
  • Trypsin Inhibitors / analysis
  • Trypsin Inhibitors / metabolism
  • alpha-Amylases / antagonists & inhibitors*


  • Enzyme Inhibitors
  • Plant Proteins
  • Toll-Like Receptors
  • Trypsin Inhibitors
  • Glutens
  • alpha-Amylases