Project

The main objective of CD3DTech-CM is to develop the technological basis for creating a high-throughput nutraceutical screening platform that serves [1] to understand multimodal variability in gluten-free diet response, [2] as the basis for developing and offering personalized dietary advice, and [3] to evaluate personalized nutraceuticals to resolve or mitigate persistent symptoms in celiac disease patients after long-term adherence to a gluten-free diet. The specific objectives of the project are:
SO1. Deep phenotyping and comprehensive characterization of celiac disease patients with different responses to the gluten-free diet, categorizing patients based on multimodal variability in CD3DTech-CM measurements and response to the gluten-free diet, considering symptom persistence, nutritional patterns, molecular background (i.e., immune system), and host-microbiome interactions to develop personalized nutritional recommendations facilitating the achievement of goals set in SO2 and SO4;
SO2. Develop multilevel and multiscale approaches to model the response of non-responsive celiac disease to nutraceuticals, using systems biology and artificial intelligence techniques to create in silico models for holistic understanding. This will create comprehensive computer models that explore complex relationships between the host and gut microbiome, considering microbiome composition, metabolome profiles, dietary patterns, nutritional status, and immunological profiles. These approaches will serve as powerful tools to develop the high-throughput screening platform for nutraceuticals capable of modulating the gut microbiome;
SO3. Establish pioneering organoid and gut-on-chip models for non-responsive celiac disease patients, generating a pioneering biological resource to gain unique insights into the complex cellular and molecular mechanisms in gluten-free diet failure. These models will serve as an ideal framework to evaluate the effects of precision nutraceuticals on gut barrier dynamics and its components, with special emphasis on the gut microbiome, considering individual patient characteristics;
SO4. Determine the complexity of personalized responses to nutraceuticals in non-responsive celiac disease, integrating the in vitro models developed in SO3 with the in silico approaches created in SO2 to create the comprehensive high-throughput screening platform of CD3DTech-CM, which will evaluate Precision Nutrition products (i.e., personalized nutraceuticals) specific to non-responsive celiac disease patients.
The project will be developed by a consortium that brings together 4 partners and 2 associated entities. This consortium includes a research centre specializing in precision nutrition and computational biology (IMDEA Alimentación), a hospital with experts in the management and treatment of celiac disease (Hospital Universitario Infanta Sofía), a research centre specializing in the development of 3D in vitro cell models (Centro de Investigación Biomédica en Red), and a university with experience in clinical nutritional studies (Universidad Europea de Madrid), along with a hospital (Hospital de La Paz) and a celiac patient association (Asociación de Celíacos y Sensibles al Gluten) as associated entities.