Authors
Jorge Pardellas1,2, Rita Vilaça3, Ricardo Dias3, Susana Soares3, María Rosa Pérez-Gregorio*1,2,3
1 Institute for Agroecology and Food (IAA), Universidade de Vigo – Campus Auga, Food and Health Omics, 32004 Ourense (Spain)
2 Galicia Sur Health Research Institute (IIS Galicia Sur). SERGAS-UVIGO (Spain)
3 LAQV-REQUIMTE. Department of Chemistry and Biochemistry. Faculty of Sciences. University of Porto. Rua do Campo Alegre s/n 4169-007 Porto (Portugal)
Corresponding author: María Rosa Pérez-Gregorio
Celiac disease is an autoimmune disease triggered in genetically predisposed individuals after gluten protein ingestion. Gluten is a protein naturally present in some grains, such as wheat, rye or barley, but it is also frequently added to processed food to add protein, texture and flavour. The rising number of people affected by celiac disease and gluten sensitivity, and the lack of treatments, aside from following a gluten-free diet, highlight the need for more research. The WHEATBIOME project will investigate grain production improvements as well as novel food processing to improve the quality of life of millions of people around the globe affected by gluten-derived diseases.
Gluten: a demonized ingredient in occidental diets
The general trend in gluten consumption varies among different groups and individuals. A trending movement about gluten-free foods is running among different groups and individuals in occidental societies, related also with an increased interest of consumers about the benefits of healthy diets. These trends are shaping the food industry to answer consumer’s choices and necessities [1]. Under this context, an increasing seek for information regarding the potential harnessing effect of gluten consumption is observed, connected with an increase in the prevalence of celiac disease and non-celiac gluten hypersensitivity. Beyond those consumers with medical reasons for avoiding gluten, this general trend concludes in an adoption of a gluten-free lifestyle driven by a lack of deep understanding of gluten real effects, and sometimes improper perception of what a healthy diet must be. This group often includes individuals who follow popular diet trends or believe that eliminating gluten can help with weight loss, digestive issues, or overall well-being. However, for those individuals without any immune reaction to gluten, consumption of gluten-containing cereals, such as wheat, barley, rye or oats has no associated any risks and may even promote digestive health by providing dietary fibre and other bioactive compounds with prebiotic activity and essential nutrients such as minerals or vitamins (mainly from B-group) [2].
Overall, maintaining a diverse diet is essential to keep a general status of good health and well-being. Nevertheless, considering the high prevalence of celiac disease and non-gluten hypersensitivity, novel strategies must appear on the horizon to promote a healthy, sustainable, and tasty diet for people affected by gluten.
Differences between Celiac Disease and Gluten Sensitivity
Understanding the current situation leading to the vilification of gluten among a growing population is crucial for comprehending the underlying mechanisms of these prevalent non-communicable diseases. Gluten ingestion has been associated with various immune responses, including non-celiac gluten sensitivity and celiac disease.
Gluten is a protein naturally present in some grains, such as wheat, rye, or barley. During digestion, proteins are proteolyzed: they are processed into smaller components, known as peptides. Gluten proteins possess distinctive structural characteristics that make them highly resistant to gastrointestinal breakdown, notably a high content of proline and glutamine residues. In most individuals, gluten is properly processed and broken down into harmless small peptides.
However, when gluten proteins are inadequately digested, as happens in individuals with non-celiac gluten sensitivity, larger peptides result from proteolysis, lingering for extended periods in the intestine and triggering negative effect on the body, such as oxidative stress reactions and inflammation [2].
On the other hand, individuals who suffer from Celiac Disease undergo a different reaction mechanism. Celiac Disease is an autoimmune disorder where the immune system of the patient recognizes specific motifs present in gluten-derived peptides, that trigger an immune response in the individual. These peptides are identified by antigen-presenting cells, setting off a cascade of immune system events culminating in T-cell proliferation, the production of proinflammatory cytokines, and the activation of antigliadin antibodies. These antibodies proceed to target and damage the enterocytes, resulting in villous atrophy and crypt hyperplasia, which are significant forms of intestinal injury[3]. These processes result in weakening the intestinal barrier of individuals with celiac disease and it is manifested by symptoms such as abdominal discomfort, bloating, diarrhea, and impaired nutrient absorption[4].
Research on factors affecting gluten content in grains is still much needed
Gluten is a highly complex group of storage proteins mainly present in cereal grains like wheat. Its proteins are mainly divided in gliadins and glutenins. To date, hundreds of gluten proteins have been already described and grouped based on molecular features into alpha-, beta-, gamma- or omega-gliadins and high- or low-molecular-weight glutenins[5]. Although several immunogenic and toxic peptides have been described, the structural similarity among gluten proteins clearly difficult the proper identification of new toxic peptides. Moreover, the overall content and relative proportions of these gluten types in different grains vary considerably, depending on different genetic and environmental factors. Among the environmental factors, the effect of microbiota, the community of microorganisms that live on and within wheat plants, on gluten content in grain production is still unknown.
The WHEATBIOME project aims at understanding the role of microbiota in wheat plant and grain development, with special emphasis on the effect on gluten content. Thorough research on different wheat genetic varieties as well as the diverse associated microbiome compositions will lead to understand the effect of wheat microbiome on the plant and the grain. The WHEATBIOME project ultimately aims at wide approach from soil to plate, obtaining a sustainable, healthy, and tasty wheat with a proper nutritional quality, the lowest possible immunogenic protein content, and higher bioactive compounds, such as natural antioxidants.
Better agricultural practices for better wheat grains
As storage proteins, gluten is produced in plants during nitrogen (N) metabolism, a crucial functional activity in plants for grain protein formation and accumulation [6]. The primary and secondary metabolism in plants is generally influenced by the environment, as mentioned before[7]. However, there remains a dearth of knowledge concerning the metabolic enzymes in grains related to N metabolism, and how different biotic (microorganisms) and abiotic (e.g., rain) factors can affect their activities, [8]. To date, the impact of nitrogen[9] or sulfur fertilization[10] as well as the infections such as mildew[11], have been described as affecting the activity of several enzymes implicated in protein synthesis. In parallel, soil-plant microbiota crosstalk and its implications on plant metabolism have been recently studied as playing a pivotal role in the general biological activity of plants [12]. However, the implications of the type of soil, wheat varieties, weather conditions, and agronomic practices on microbiota composition, soil-plant interactions, plant metabolism, and ultimately the nutritional quality and immunogenic protein expression in wheat remain unexplored.
The use of microorganisms such as plant growth-promoting biofertilizers, is one promising possibility to enhance sustainability and reduce the use of conventional fertilizers and pesticides during plant cultivation[13]. Through their interaction with plant roots, they can increase plant productivity without compromising the nutritional quality of plants, but the effects of the different microbial ecosystems on wheat grain quality have been unexplored so far. Significant progress has been made in studying the effects of various biotic and abiotic factors on wheat composition. However, challenges arise from the variability in experimental setups, environmental conditions, and the varieties under study, making it difficult to establish clear comparisons.
The WHEATBIOME project aims to correlate different agronomic parameters, including soil type, fertilization, irrigation, and wheat varieties, with the ecology and function of soil and wheat microbiota. It also seeks to understand their impact on the nutritional quality of grains, with a particular focus on the synthesis of bioactive compounds and immunogenic proteins. This involves designing a complex bioinformatics tool to support decision-making in selecting the best agricultural practices: from selecting the wheat varieties for cultivation for specific wheater conditions to growing the wheat under the best sustainable farming practices, aiming to achieve low immunogenicity and high bioactivity in wheat products.
Gluten Consumption-Food Industry Crosstalk
A paradox exists between the widespread reduction in gluten consumption and the pervasive presence of gluten proteins in the food industry. The specific features of gluten proteins that trigger celiac disease are those related to their outstanding technological properties. Gluten has a pivotal role in the texture, structure, and elasticity of wheat-based products, such as bread, pasta, cakes, and pastries. Furthermore, gluten helps improve the overall quality and appearance of baked goods by providing structure and preventing crumbling. It also contributes to the chewiness and moistness of certain products, enhancing their sensory appeal [13].
Wheat flour utilized for bread production typically requires a protein content exceeding 10%, equating to more than 8% of gluten proteins. This high protein content is crucial for ensuring the desired end-use quality. Sufficient gluten proteins are necessary to facilitate the formation of a cohesive protein network within the dough, essential for stabilizing gas bubbles in leavened doughs and creating porous structures in baked products[14].
However, due to an increasing demand for gluten-free options, food manufacturers are developing alternative ingredients and production methods to cater to this segment of the market. Following a gluten-free diet is associated with an economic burden and can lead to social exclusion. Furthermore, considering the presence of gluten proteins in the food industry, cross-contamination is still a problem in many products. Moreover, some malnutrition problems can arise from avoiding a huge list of food from our diet and in some cases, following a gluten-free diet is not sufficient to revert intestinal damage in celiac disease patients[15]. Under this context, is imperative to establish novel strategies helping to control the increase in the prevalence of immune reactions to gluten, while deepening our knowledge of the factors influencing gluten immunogenicity. It is important to raise societal awareness that not all gluten proteins are immunogenic proteins and only the toxic or immunogenic proteins are responsible for the different (auto)-immune conditions.
To date, different therapeutic approaches have been used help people manage gluten sensitivity or immune reactions such as degradation/neutralization of gluten e.g. by enzyme therapy, gluten-sequestering polymers); epithelium intestinal barrier enhancing therapies (e.g. zonulin antagonists); immune targeted therapies (e.g. glucocorticoids with low systemic bioavailability, peptide-based immunotherapy, inhibition of tTG2, blocking HLA-DQ2 or HLA-DQ8, blocking intestinal homing of inflammatory cells, cytokine therapy, etc.) or microbiota and nematode-based therapies (e.g. probiotics that help in the gluten breakdown)[16]. However, the research findings about these therapeutic strategies are not conclusive. Recently, the use of bioactive compounds such as polyphenols has been standing out as a promising alternative since they possess anti-inflammatory and antioxidant properties and they possess the ability to bind to celiac disease-related immunogenic peptides affecting the digestion, bioavailability, and immune response[17].
Food components are not consumed alone and to date the molecular interactions between the different ingredients in the development of novel food products remain largely unexplored. Recent findings pointed out the clear influence of interaction between the different food components, such as bioactive compounds-immunogenic proteins on the biological assumption of food[18-20]. Moreover, the host-food microbiota interaction can clearly impact food matrix interactions, ultimately affecting the health status and human well-being.
The WHEATBIOME project aims to use a multidisciplinary approach to gain new insights into the use of specific agronomic conditions and environments for the production of wheat with low immunogenicity but high nutritional quality. This endeavour seeks to further explore the role of autochthonous microbiota in designing healthy and tasty wheat-based foods, with minimal impact on the immune system. Its overarching aim is to contribute to the development of gluten-based foods as alternatives for people with celiac disease.
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