Dietary wheat amylase trypsin inhibitors exacerbate murine allergic airway inflammation

Eur J Nutr. 2019 Jun;58(4):1507-1514. doi: 10.1007/s00394-018-1681-6. Epub 2018 Mar 29.


Background: Wheat amylase trypsin inhibitors (ATI) are dietary non-gluten proteins that activate the toll-like receptor 4 on myeloid cells, promoting intestinal inflammation.

Aim of the study: We investigated the effects of dietary ATI on experimental allergic airway inflammation.

Methods: Mice on a gluten and ATI-free diet (GAFD), sensitized with PBS or ovalbumin (OVA) and challenged with OVA, were compared to mice on a commercial standard chow, a gluten diet naturally containing ~ 0.75% of protein as ATI (G+AD), a gluten diet containing ~ 0.19% of protein as ATI (G-AD) and a GAFD with 1% of protein as ATI (AD). Airway hyperreactivity (AHR), inflammation in bronchoalveolar lavage (BAL) and pulmonary tissue sections were analyzed. Allergic sensitization was assessed ex vivo via proliferation of OVA-stimulated splenocytes.

Results: Mice on a GAFD sensitized with PBS did not develop AHR after local provocation with methacholine. Mice on a GAFD or on a G-AD and sensitized with OVA developed milder AHR compared to mice fed a G+AD or an AD. The increased AHR was paralleled by increased BAL eosinophils, IL-5 and IL-13 production, and an enhanced ex vivo splenocyte activation in the ATI-fed groups.

Conclusions: Dietary ATI enhance allergic airway inflammation in OVA-challenged mice, while an ATI-free or ATI-reduced diet has a protective effect on AHR. Nutritional wheat ATI, activators of intestinal myeloid cells, may be clinically relevant adjuvants to allergic airway inflammation.

Keywords: Allergic airway inflammation; Amylase trypsin inhibitors; Gluten; Innate immunity; Wheat sensitivity.

MeSH terms

  • Amylases / antagonists & inhibitors*
  • Amylases / immunology
  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • Disease Models, Animal
  • Inflammation / diet therapy
  • Inflammation / immunology
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Respiratory Hypersensitivity / diet therapy*
  • Respiratory Hypersensitivity / immunology*
  • Triticum / chemistry
  • Triticum / immunology*
  • Trypsin Inhibitors / chemistry
  • Trypsin Inhibitors / immunology*
  • Trypsin Inhibitors / pharmacology*


  • Trypsin Inhibitors
  • Amylases