Understanding gluten’s role in autoimmunity and inflammation

The interaction between people and their environment, mediated by diet, plays a crucial role in regulating inflammatory responses. Chronic inflammatory diseases are on the rise and the scientific community has been actively investigating pro-inflammatory nutrients as potential therapeutic targets. Gluten, a major component of wheat, barley and rye, has been implicated in numerous health problems, most notably celiac disease (CD). This review essay summarizes the key findings of a recent study published in the Journal of Translational Gastroenterology, focusing on the pro-inflammatory effects of gluten and its implications for autoimmunity.

Gluten and its components

Gluten is a complex protein mixture consisting mainly of glutenin and gliadin. Gliadin, which contains approximately 70% of gluten, is particularly relevant in inducing harmful immune responses in Crohn’s disease. Gluten is abundant in the Western diet and can lead to a variety of adverse effects beyond Crohn’s disease, suggesting that gluten plays a broader role in inflammatory and autoimmune diseases.

Gluten-induced inflammation in celiac disease

Celiac disease is a chronic, autoimmune disease characterized by intestinal damage, activated immune systems and elevated pro-inflammatory cytokines. Gluten, especially gliadin peptides, act as a trigger for this disease. Gliadin peptides cause mucosal inflammation, epithelial damage and intestinal dysbiosis. Successful gluten withdrawal improves these inflammatory signatures, underscoring the crucial role of gluten in the pathogenesis of the disease.

Beyond Celiac Disease: Gluten and Other Autoimmune Diseases

The harmful effects of gluten extend beyond CD and affect multiple body compartments and organs. Gluten peptides can affect intestinal permeability, allowing immunogenic molecules to reach internal compartments and trigger autoimmune reactions in distant organs. The distribution of gliadin peptides to these organs leads to organ dysfunction and pathology through post-translational modifications, which convert naive peptides into immunogenic and pro-inflammatory molecules. This gluten-mediated inflammatory cascade is thought to be involved in a range of autoimmune diseases, including dermatitis herpetiformis, gluten ataxia, gluten allergy, and possibly other non-celiac autoinflammatory and neurodegenerative disorders.

The place of gluten in the human diet

Despite its pro-inflammatory properties, gluten has long been a staple of the human diet, providing dietary fiber, B vitamins and minerals. However, gluten does not contribute essential nutrients, and its avoidance does not endanger human well-being except in well-defined gluten-dependent conditions. The increasing popularity of gluten-free diets, driven by pseudoscientific claims, has had a significant impact on dietary habits. However, a gluten-free Mediterranean diet, which combines the benefits of both approaches, may be a healthier alternative.

Gluten side effects and pathogenesis

Gluten has multiple side effects, including pro-inflammatory and pro-oxidative activities, leading to intestinal disorders and inadequate health outcomes. Gliadin peptides can induce cellular stress, activate proliferative mechanisms, induce a pro-inflammatory storm, and inhibit critical ion channels and vesicular traffic. Furthermore, gluten-related changes in the gut microbiota and enhanced enzymatic modifications can lead to autoimmunity induction through molecular mimicry.

Conclusions

As a pro-inflammatory molecule, gluten plays a crucial role in celiac disease and possibly other autoimmune and inflammatory diseases. The identification of the harmful effects of gluten underlines the need for comprehensive investigation of its role in non-celiac autoimmune diseases. Gluten withdrawal may alleviate disease activity in Crohn’s disease and possibly other chronic inflammatory, metabolic, and autoimmune diseases. Although avoiding gluten may be beneficial in gluten-dependent conditions, a gluten-free Mediterranean diet is recommended to ensure overall nutritional value.

This review summarizes the key findings of the recent study on the pro-inflammatory effects of gluten and their implications in autoimmune diseases, providing insights into the mechanisms underlying gluten-mediated inflammation and potential therapeutic options.