Dr. Schär Institute Logo
A wheat field at sunset

ATI: trypsin and amylase inhibitors and gluten

What are trypsin and amylase inhibitors (ATI) in wheat and their possible role in non-coeliac gluten sensitivity via the innate immune system?

What are amylase-trypsin inhibitors (ATI) and how do they affect the body?

Trypsin and amylase inhibitors, known as ATIs (amylase-trypsin inhibitors), are proteins found in some cereals, particularly wheat.

In recent years, these proteins have attracted interest due to their possible role in non-coeliac gluten sensitivity. Although gluten has traditionally been blamed for many of the symptoms associated with wheat consumption, we now know that other components of the cereal, such as ATIs, may also be involved in certain inflammatory mechanisms.

However, their exact role has not yet been fully established, so it is important to interpret the available evidence with caution.

What are ATIs (trypsin and amylase inhibitors)?

ATIs are a family of low-molecular-weight proteins found in cereals such as wheat, barley and rye.

In wheat, gluten accounts for the majority of the protein fraction, whilst ATIs make up a much smaller proportion. Even so, their significance depends not so much on their quantity as on their biological activity.

These proteins accumulate mainly in the cereal endosperm and are particularly resistant to digestion. This resistance explains why they can reach the intestine whilst retaining some of their functional capacity.

Functions of ATIs in cereals

In cereals, trypsin and amylase inhibitors (ATIs) are not present by chance. They fulfil several important functions for the plant itself:

Non-coeliac gluten sensitivity: a diagnosis of exclusion

Non-coeliac gluten sensitivity remains a complex condition and is not yet fully defined.

Unlike coeliac disease or wheat allergy, there are currently no specific biomarkers that allow us to diagnose it directly. Consequently, a diagnosis is considered only after ruling out other disorders related to wheat or gluten.

In recent years, some authors have proposed the term ‘non-coeliac wheat sensitivity’ as well, because the symptoms may not be due solely to gluten, but also to other components of wheat, such as fructans or trypsin and amylase inhibitors (ATIs).

A hand holds a bundle of wheat and a red 'no' symbol against a plain background

The role of ATIs in non-coeliac gluten sensitivity

ATI have been proposed as one of the possible components of wheat implicated in non-coeliac gluten sensitivity. Unlike in coeliac disease, which involves well-characterised immunological mechanisms and an adaptive immune response to gluten, the activation of the innate immune system appears to play a greater role in non-coeliac gluten sensitivity.

Innate immunity and Toll-like receptors (TLRs)

Innate immunity constitutes the body’s first line of defence against external agents. Within this system, Toll-like receptors (TLRs) are involved in recognising specific signals and in triggering inflammatory responses.

Some experimental studies have suggested that wheat ATIs may activate innate immunity via these receptors, particularly TLR4. This activation would promote the production of pro-inflammatory mediators and could contribute to the onset of symptoms in susceptible individuals.

However, it is important to note that much of this evidence comes from in vitro studies or animal models. Therefore, although the mechanism is plausible, further clinical studies in humans are still needed to precisely determine its relevance.

Conclusion: what we know today about ATIs and what remains to be investigated

In short, ATIs are proteins found in wheat and other related cereals that have been shown to activate innate immune mechanisms in experimental studies.

For this reason, they are considered possible contributors to the symptoms attributed to non-coeliac gluten sensitivity or, more broadly, to non-coeliac wheat sensitivity.

However, the available evidence does not yet allow us to conclude that ATIs are solely responsible for these symptoms. It is likely that various components of wheat and different mechanisms are involved in this condition, including other elements such as fructans and individual patient factors.

Therefore, the role of ATIs should be understood as a relevant but still open line of research.

Frequently asked questions

Author

Miguel Ángel Lurueña

PhD in Food Science and Technology

Yo may also be interested in...

Sources

Referencias

  1. Reig-Otero Y, Mañes J, Manyes L. Amylase-Trypsin Inhibitors in Wheat and Other Cereals as Potential Activators of the Effects of Nonceliac Gluten Sensitivity. J Med Food. 2017.
  2. Ryan CA. Protease inhibitors in plants: genes for improving defenses against insects and pathogens. Annu Rev Phytopathol. 1990;28:425-449.
  3. Barbaro MR, et al. Recent advances in understanding non-celiac gluten sensitivity. F1000Research. 2018.
  4. Sapone A, et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Medicine. 2012;10:13.
  5. Shannahan S, Leffler DA. Diagnosis and updates in celiac disease. Gastrointest Endosc Clin N Am. 2017;27(1):79-92.
  6. Catassi C, Elli L, Bonaz B, et al. Diagnosis of non-celiac gluten sensitivity: the Salerno Experts’ criteria. Nutrients. 2015;7:4966-4977.
  7. Volta U, Caio G, De Giorgio R, et al. Non-celiac gluten sensitivity: a work-in-progress entity in the spectrum of wheat-related disorders. Best Pract Res Clin Gastroenterol. 2015;29:477-491.
  8. Thomas KE, Sapone A, Fasano A, et al. Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent. J Immunol. 2006;176:2512-2521.
  9. Fasano A. Zonulin and its regulation of intestinal barrier function. Physiol Rev. 2011;91:151-175.
  10. Schuppan D, Zevallos V. Wheat amylase trypsin inhibitors as nutritional activators of innate immunity. Dig Dis. 2015;33(2):260-263.
  11. Junker Y, Zeissig S, Kim SJ, et al. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. J Exp Med. 2012;209:2095-2108.