Molecule of the Month: Gluten

Breads, pastries and cakes are foods humans have been making and devouring for centuries. In particular, bread has been a central staple of our diet as scientists in 2018 discovered evidence of bread-making from a 14,000-year-old dig site1.

One central component to breads and other baked goods is gluten. This molecule able to provide unique structure and stability that produces the moreish crumb we are all too familiar with. However, the wonders of gluten do not stop there, as many individuals who avoid meat also use high gluten mixtures as a meat substitute.

Nevertheless, it is important to note that gluten is not well-tolerated within some individuals and can even manifest as celiac disease, a condition where the immune system responds to gluten molecules. Although, gluten free diets are the only means for controlling intolerances, they have become popularised to those not sensitive to gluten. Even though gluten free foods may be perceived by the general public as being healthier to aid weight loss, the scientific evidence is inconsistent presenting great uncertainties with these claims.

Grains to Gluten

Gluten is a protein stored within a wide variety of grains such as wheat, barley and rye to support germination and seedling development2. Grains, especially wheat, are made up of three distinct parts (Figure 1)3 named the embryo, endoplasm, and bran. While the embryo ensures the formation of the next generation, the endosperm stores gluten and starch to support and nourish future development4

Figure 1: The structure of grains include the bran, endosperm and germ which all have a function to ensure the viability of the next generation of plants.

Gluten does not define a singular protein within the wheat, but instead, forms the basis of a complex mixture of related, yet distinct proteins5. Although, there are many sub-categories of gluten, the two main biochemical groups are gliadin and glutenin.

Complex structures

Gluten is widely utilised in baking as it is able to act as a binding agent and is used within processed foods to improve both flavour and texture. However, bread predominantly relies on the tight knit, springy texture that gluten provides through various bonds.

The structure of dough is down to a range of chemical interactions such as hydrogen, ionic and covalent bonds. Hydrogen bonds, an interaction between a hydrogen and another atom, takes place when the gluten is hydrated. Generally, hydrogen bonds are weak in isolation, but with the process of kneading, more bonds are able to form between the gluten (Figure 2)7 and end up contributing significantly to the stability of the dough8.

Figure 2: Shows when gluten (orange) is hydrated and stretched that important interactions, such as hydrogen bonds (black), are able to form giving rise to the tight knit structure of bread.

These unique properties of gluten rests on the ratio of gliadin and glutenin as both are needed to contribute to the desired structure and crumb of baked bread. For example, the hydrated form of gliadin contributes to the viscous and extendable nature of the dough whereas, hydrated glutenin is responsible for both the strength and elasticity of the mixture6. Gluten is also heat resistant, meaning that the dough still retains these properties, upon baking or boiling.

Coeliac Disease

Gluten is able to provide the structure and elasticity sought after in bread and pasta doughs, however, some individuals cannot tolerate gluten and can fall under a whole range of diseases termed gluten related disorders. Although, each of the diseases are related to one another, they are distinct within their manifestation, the most well-known of which is coeliac disease9.

Coeliac disease is classified as an autoimmune disorder where there is chronic inflammation of the intestine10 . An autoimmune disorder is a collection of diseases where the immune system attacks your own cells and classifies harmless molecules as an organism that causes disease11,.

In this case, coeliac disease triggers an immune response towards both gluten molecules and intestinal tissues.12 Just like many other autoimmune disorders, the causes of the disease are multifactorial where genetic and environmental factors interact with one another13.

The inappropriate activation of the immune system towards gluten is marked with the production of antibodies, release of inflammatory chemicals and expansion of immune cells that leads to structural damage (Figure 3)14 of the small intestine15,10. This damage is generally caused by the adaptive arm of the immune system which is known to be highly specific and long-lasting thus, mirroring the aggressive nature of gluten intolerances or allergies16.

Figure 3: Shows the normal (A) small intestine structure and damaged structure (B) resulting from untreated celiac disease.

However, there is also emerging evidence that the innate arm of the immune system may contribute to the progression of the disease17. The innate immune system is made up of a group of specialised cells that are considered as the “first line of defence” when responding to signals of danger from the body18. Gluten peptides are wrongly characterised as “danger” by the body, within Coeliac disease, and studies have shown gluten exposure has resulted shown an increase in eosinophil protein and histamine secretion19.

Gluten free, for all?

For patients with coeliac disease, the only treatment is the avoidance of gluten within the diet entirely. However, gluten free diets have become increasingly popular among the general population who have no reported sensitivities against gluten. This is mainly due to the fact that they are perceived as a healthier choice by the consumer. In 2013, a study found that 65% of Americans think gluten free foods are healthier and 27% of those actually go onto choose these products for the purpose of weight loss20.

A UK study of 40,000 individuals that estimated gluten intake in relation body fat found a decrease of fat percentage in males who had less gluten. However, females who had less gluten showed an increase within fat percentage within presenting a sex difference even after controlling for all other factors21. Although, this may seem significant, the association between gluten and body fat is not clinically relevant. This is mainly because the percentage change of body fat in the sexes are so minute that it is unlikely to provide any benefit to the wider population.

Science in conflict

Many of the studies which measure gluten intake, in relation to metabolic health, present conflicting evidence. A randomised control study presented that low-gluten diets, compared to high gluten ones, resulted in moderate but significant weight loss, over an eight-week period22. Conversely, a related study showed that there was no significant decrease in body weight in the gluten free diet group when compared to a control diet23.

This highlights great uncertainty to whether gluten free diets can provide any weight-loss or health benefit to those who are not sensitive or allergic to gluten. It is particularity important to note, that gluten free foods generally contain lower levels of protein, fibre, iron, vitamins and higher levels of calories, which may stem any nutritional benefit to those who can tolerate gluten24.

Overall, gluten is a wonderous and weird molecules which utilises various chemical bonds to provide the structure within baking. The adaptive arm of the immune system plays a large role in Coeliac disease, however, these is emerging evidence that the innate system may contribute to the progression of the disease. Although there is a big market for gluten free diets in those without sensitivities, the perceived health benefit may be overstated.


1.         Prehistoric bake-off: Scientists discover oldest evidence of bread. BBC News (2018).

2.         Shewry, P. What Is Gluten—Why Is It Special? Front. Nutr. 6, (2019).

3.         The European Food Information Council. Whole Grains.

4.         Tosi, P., Gritsch, C. S., He, J. & Shewry, P. R. Distribution of gluten proteins in bread wheat (Triticum aestivum) grain. Ann. Bot. 108, 23–35 (2011).

5.         Biesiekierski, J. R. What is gluten? J. Gastroenterol. Hepatol. 32, 78–81 (2017).

6.         Wieser, H. Chemistry of gluten proteins. Food Microbiol. 24, 115–119 (2007).

7.         Reuben, B. Bread chemistry on the rise. Chemistry World

8.         Sivam, A. S., Sun-Waterhouse, D., Quek, S. & Perera, C. O. Properties of Bread Dough with Added Fiber Polysaccharides and Phenolic Antioxidants: A Review. J. Food Sci. 75, R163–R174 (2010).

9.         Akhondi, H. & Ross, A. B. Gluten And Associated Medical Problems. in StatPearls (StatPearls Publishing, 2021).

10.       Parzanese, I. et al. Celiac disease: From pathophysiology to treatment. World J. Gastrointest. Pathophysiol. 8, 27–38 (2017).

11.       Smith, D. A. & Germolec, D. R. Introduction to immunology and autoimmunity. Environ. Health Perspect. 107, 661–665 (1999).

12.       López Casado, M. Á., Lorite, P., Ponce de León, C., Palomeque, T. & Torres, M. I. Celiac Disease Autoimmunity. Arch. Immunol. Ther. Exp. (Warsz.) 66, 423–430 (2018).

13.       Ceccarelli, F., Agmon-Levin, N. & Perricone, C. Genetic Factors of Autoimmune Diseases 2017. J. Immunol. Res. 2017, (2017).

14.       NeuroRelief. To Wheat or Not to Wheat: May is Celiac Disease Awareness Month. The NEI Connection (2013).

15.       Gianfrani, C., Auricchio, S. & Troncone, R. Adaptive and innate immune responses in celiac disease. Immunol. Lett. 99, 141–145 (2005).

16.       Alberts, B. et al. The Adaptive Immune System. Mol. Biol. Cell 4th Ed. (2002).

17.       Dunne, M. R., Byrne, G., Chirdo, F. G. & Feighery, C. Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder. Front. Immunol. 11, (2020).

18.       Hato, T. & Dagher, P. C. How the Innate Immune System Senses Trouble and Causes Trouble. Clin. J. Am. Soc. Nephrol. CJASN 10, 1459–1469 (2015).

19.       Lavö, B. et al. Challenge with gliadin induces eosinophil and mast cell activation in the jejunum of patients with celiac disease. Am. J. Med. 87, 655–660 (1989).

20.       Jones, A. L. The Gluten-Free Diet: Fad or Necessity? Diabetes Spectr. Publ. Am. Diabetes Assoc. 30, 118–123 (2017).

21.       Behrendt, I., Fasshauer, M. & Eichner, G. Gluten intake and metabolic health: conflicting findings from the UK Biobank. Eur. J. Nutr. (2020) doi:10.1007/s00394-020-02351-9.

22.       Hansen, L. B. S. et al. A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults. Nat. Commun. 9, 4630 (2018).

23.       Ehteshami, M. et al. The Effect of Gluten Free Diet on Components of Metabolic Syndrome: A Randomized Clinical Trial. Asian Pac. J. Cancer Prev. 19, 2979–2984 (2018).

24.       Kutlu, T. Gluten-free diet: is it really always beneficial? Turk. Arch. Pediatr. Pediatri Arş. 54, 73–75 (2019).

Image credit:

Bread and wheat image by Mariana Kurnyk from Pexels

Wheat field image by Pixabay from Pexels

Dough kneading image by ROMAN ODINTSOV from Pexels

Person clutching stomach image by Sora Shimazaki from Pexels

Gluten free image by Henri Mathieu-Saint-Laurent from Pexels

Document discussion image by Alexander Suhorucov from Pexels

Flour split image by monkik from

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