Project ATI-DETOX Modification of functional properties of Amylase Trypsin Inhibitors by REDOX reactions to mitigate pathogenic effects

Projectnummer
LWV20187

Missie
D. Gewaardeerd, gezond en veilig voedsel

MMIP primair
D2. De consument, duurzame en gezonde voeding in een groene leefomgeving

MMIP secundair

Startdatum project
01-01-2021

Einddatum project
31-12-2026

Projectleider
Henk Schols

Website

Status project

Samenvatting project
50-300 million people in the western world are affected with irritable bowel syndrome (IBS) or non-celiac wheat sensitivity (NCWS). There is broad scientific consensus that gluten is not the main cause of these pathologies and that other components in wheat, called Amylase Trypsin Inhibitors (ATIs), can play an important role. Partially informed by social media and due to lack of scientific mechanistic proof, consumers tend to avoid cereal-based products, which generally are the most important and cheap source of nutrients in our diet. Human in vitro and in vivo mice model studies have shown that ATIs play an important mechanistic role in IBS and NCWS, initiating intestinal inflammation and adaptive immune responses. ATIs are also the main allergens causing bakers asthma and eczema. ATIs account for about 5-15% of the total wheat grain proteins and up to two thirds of the water-soluble (albumin) protein fraction. ATIs are part of a large family of enzyme inhibitors in plants, that is characterized by a very stable protein structure (due to disulphide bridging) which confers protection to processing and gastrointestinal degradation. The redox status of ATIs has been shown to be a switch knob for its biofunctionality in various ways:

• Partial reduction of disulfide bonds in ATIs can double amylase and papain enzyme inhibition, but full reduction allows degradation by the intestinal enzyme trypsin.
• Allergenic properties as baker’s eczema can be mitigated when ATIs are reduced by the thioredoxin/thioredoxin reductase system.

Higher structural disulphide bond reactivity of ATIs are linked to increased dough stiffness in bread dough processing. Fermentation conditions (yeast vs sour dough) and recipes (high pH in cakes/biscuits vs lower pH in bread) have an effect on the reactivity of thiol groups.
Here we propose to elucidate the role of redox status of ATIs on in vitro digestibility, intestinal cell binding, cell modulation and immunomodulation, and cereal bioprocessing. Different approaches to modify the disulphide bridges of ATIs in an isolated fraction and in situ during wheat food processing will be applied. The outcomes will be used to design clinical studies in which the pathological effects of partially reduced ATIs on the gut will be studied. The elucidation of this role will be pivotal to mitigate the pathological effects of ATIs to reduce consumer concerns and promote consumption of wheat-based food products.

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