Dietary Polyphenol's Role in the Prevention of Celiac Disease

Celiac Disease (CD) is a serious global public health problem. Given its high prevalence and the lack of therapeutic alternatives to a strict gluten-free diet, the research and development of new solutions capable of improving the quality of life of celiac patients is a priority.Polyphenolic compounds (PCs) are probably the most important group of non‑nutritive bioactive substances in the human diet, found in fruits, vegetables, grains, spices, herbs, and derived products. Several epidemiological, clinical, and nutritional studies suggest that polyphenols have enormous potential in promoting human health by modifying disease risk profiles through the modulation of various biological pathways. At present, several molecular and cellular targets responsive to polyphenol action have already been identified, as well as their implications in the context of cancer, cardiovascular diseases, chronic inflammation, and metabolic disorders. The action of dietary polyphenols in CD, however, remains unexplored. Thus, this project aims to characterize the chemistry and biochemistry of dietary polyphenols in the context of CD, assessing their antioxidant and anti‑inflammatory activity and the molecular mechanisms through which they may promote symptom alleviation. With a deeper understanding of how dietary polyphenols modulate CD, it will be possible to develop an effective nutritional intervention and an alternative prevention strategy to a gluten‑free diet, promoting the formulation of new functional foods enriched with polyphenols. In general, the proposed work includes the isolation of PCs from various food sources (apples, green tea, grapes, elderberries) and from by‑products of the food industry (wine and cork industries). These compounds will be tested in vitro to determine their ability to modulate oxidative damage and inflammatory responses triggered by gluten bioactive peptides. These peptides will be obtained through simulated gastrointestinal digestion of wheat gluten proteins and subsequently fractionated by preparative HPLC. The results obtained up to that point will then be corroborated in vivo, using a transgenic mouse model of CD fed with a gluten‑containing diet enriched with polyphenolic extracts and pure compounds. Additionally, the project aims to characterize, in vitro and in silico, the interaction between dietary polyphenols and gluten bioactive peptides, with particular interest in the forces involved and their dependence on structural and environmental parameters. This project seeks to promote high‑level research in several priority areas of the Horizon 2020 programme, namely health, well‑being, and sustainable agriculture, and is supported by the expertise of a multidisciplinary research team resulting from collaborations with national institutes, companies, and an international organization.