Amylase trypsin inhibitors

Amylase trypsin inhibitors were first studied in the 1940s. They are well characterized as allergens, particularly in baker's asthma (a respiratory allergy to inhalation of wheat flour) and baker's eczema, but also in food allergies to wheat. Recently, there has been renewed interest in ATIs as they are thought to play an etiologic role in celiac disease and non-celiac wheat sensitivity (NCWS).

Amylase trypsin inhibitors, or ATIs for short, are plant proteins that play a role in germination, among other things, and protect the plant from predators. They are found in all wheat varieties. ATIs block the starch-degrading enzyme amylase and the protein-degrading enzyme trypsin. Amylase breaks down starch, which serves as a carbohydrate store, into glucose and thus makes the most important source of energy available to the seedling.

Wheat ATIs can trigger symptoms inside and outside the intestine in patients with inflammatory diseases. ATIs activate the intestinal immune system and trigger inflammation, which can worsen chronic inflammatory diseases such as rheumatism or Crohn's disease. It is suspected that they are one of the causes of non-celiac wheat sensitivity if there is a corresponding intolerance. ATI sensitivity cannot yet be detected with a specific blood test

ATIs are also found in other cereals that are related to wheat, such as rye, spelt, emmer, barley, einkorn and khorasan wheat. The ATI content can vary considerably depending on the location and variety. Cereals that are not related to wheat can also contain ATIs: for example buckwheat, teff, soy, millet. However, the molecular structure of these ATIs differs from that of wheat ATIs.

ATIs occur in several isoforms, which differ in the amounts present in the different wheat varieties (including ancient and modern wheat varieties). The measurement of ATIs and their isoforms is an analytical challenge, as is their isolation (Geisslitz S et al. 2022). ATIs are associated with adverse reactions to wheat exposure, e.g. respiratory and food allergies as well as inflammatory bowel reactions associated with celiac disease and non-celiac wheat sensitivity.

Note: The majority of wheat grown worldwide is hexaploid wheat (Triticum aestivum L., also known as "bread wheat", "soft wheat" or "common wheat"), about 5% is tetraploid durum wheat (Triticum durum, also known as "pasta wheat" or "durum wheat"). Hexaploid wheat and durum wheat have been bred through intensive breeding, particularly in the last 60 years. It has been mentioned in scientific, popular and social media that the focus of modern breeding on increasing yield, improving resistance to fungal diseases and improving processing quality has resulted in reduced nutritional quality and increased levels of "natural pesticides", including ATIs. Similarly, it has been suggested that older wheat varieties (often referred to as 'ancient' and 'historical' wheats) contain lower levels of ATIs (Zevallos VF et al. 2017). There is also evidence to the contrary for the latter!

Wheat allergy: The classic food allergy to wheat has a low prevalence and is more likely to occur in children prevalnece of about 9%), who usually outgrow the allergy, resulting in an estimated prevalence of 0.1% to 0.3% in adults (Nwaru B et al. (2014). Many proteins, including a number of isoforms of ATIs, have been associated with triggering a response in challenges leading to high levels of the corresponding immunoglobulin E (IgE) (Šotkovský P et. al. 2011). However, ATIs are not associated with the most severe allergic reaction to wheat (anaphylaxis), in which gluten proteins are the main players (Scherf KA et al. 2016).

An allergic reaction to ATIs plays a role in baker's asthma. This is the most common occupational allergy in many countries (e.g. 40% of bakers in England are affected). It is a typical respiratory allergic reaction characterized by elevated IgE levels against a number of proteins, especially ATIs, but also gluten proteins. However, patients with baker's asthma can tolerate the consumption of wheat bread (Armentia A et al. 2009). In vitro studies suggest that ATIs can trigger innate enteric immune responses. This hypothesis requires further study.

Celiac disease: Autoimmunological celiac disease (CD) mediated by an inflammatory T-cell response is the most widespread and best characterized adverse reaction to gluten consumption. The identification of wheat gluten proteins as the main trigger of CD dates back to the 1950s. Since then, about 40 CD-active peptides (short amino acid sequences -epitopes- recognized by the immune system) have been identified in wheat gluten proteins (gliadins and glutenins) and related proteins from barley and rye (Sollid LM et al. 2020). However, other proteins such as ATIs have also been identified that may play a triggering role in CD (Junker Y et al. 2012; Zevallos VF et al. 2017). Although gluten proteins are the main triggers of CD, the role of other proteins and triggers including amylase trypsin inhibitors is less clear and requires further research (Geisslitz S et al. 2022).

Non-Celiac Wheat Sensitivity(NCWS): Adverse effects occur after the consumption of wheat products that are not due to celiac disease. These include gastrointestinal symptoms such as bloating and diarrhea/loose stools, but also more general symptoms such as fatigue, headaches, muscle and joint pain, depression and anxiety (Brouns F et al. 2019). However, the diagnosis of NCWS is difficult in practice, as most patients self-diagnose and the exact prevalence is therefore difficult to determine. Therefore, even scientifically based estimates vary widely, ranging from <1% to around 10% of the population (Sapone A et al. 2012).

FODMAPs: FODMAPs, the acronym for "fermentable oligosaccharides, disaccharides, monosaccharides and polyols" are sugars that are poorly absorbed in the small intestine but fermented in the large intestine, are suspected to be another cause of NCWS symptoms (Laatikainen R et al. 2017). However, there is a general consensus that FODMAPs can lead to intestinal symptoms due to gas formation/flatulence and osmotic effects/laxation, but that these symptoms are not specific to wheat FODMAPs (Geisslitz S et al. 2022).

Although there is no generally recognized definition of "old" wheat varieties, the term is usually applied to three wheat varieties that were once widely grown but are now only cultivated to a limited extent due to their relatively low yields. These are diploid einkorn, tetraploid emmer and hexaploid spelt.

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