Machine Learning Approach to Study the Interactions Between Environment and Intestinal Tissue Homeostasis in IBD

Overview

The intestinal epithelial barrier is one of the most important security checkpoints of our body that constrains harmful factors from invading mucosal surfaces and facilitates the absorption of nutrients and water. Its correct functioning is essential for maintaining gut tissue homeostasis and proper immunity. However, such an equilibrium may be interrupted, resulting in an uncontrolled entrance of pathogenic stimuli that in turn activate a persistent gut immune response, with detrimental consequences for both local and systemic immunity. Alterations in the composition and functionality of the gut microbiome seem to be a central factor in affecting gut barrier integrity thus influencing intestinal permeability. The microbiome composition is impacted by dietary habits and environmental pollution and conditions, hygiene, genetic asset, and physical activity, which could interact in concert leading to dysbiosis, thereby influencing the immune response through the production of several metabolites. Chronic inflammatory diseases, including ulcerative colitis (UC) and type 1 diabetes (T1D), share microbiota dysbiosis, among pathologic characteristics, that may arise, be provoked, or be exacerbated because of barrier leakage. Therefore, these two chronic diseases may be considered prototype pathologies where the intrinsic connection between intestinal dysbiosis and the barrier leakage impact each other during the pathogenesis.

This is an observational multicentre study performed on patients with an established diagnosis of UC (according to the standard classification) and patients with new-onset type 1 diabetes (T1D) which aims to identify environmental and genetic factors contributing to chronic inflammation within the intestine and in peripheral organs by taking advantage of Internet-Of things (IoT) technologies (web app) and machine learning approaches. During the colonoscopy procedure planned for patients with UC following the routine surveillance according to the normal clinical practice (0 and 12 months), the gastroenterologist will collect 8 additional biopsies; furthermore, blood samples and stools for UC patients and blood samples, stools, and urines for T1D patients will be collected at baseline and during the routine surveillance according to the normal clinical practice (0, 6, and 12 months) and stored for the following analysis. For T1D patients, blood, urine and stool sample collection are not planned for the normal clinical practice, but will be performed specifically for this research proposal at different points during the normal clinical practice clinical visit: baseline, after 6 months and after 12 months. For UC patients, blood and biopsies are collected during the procedures already planned for normal clinical practice during clinical surveillance. The investigators will take advantage of this standard of-care procedures to collect an additional volume of blood (at baseline, after 6 months and after 12 months). Therefore, patients expressing their voluntary participation in the study will be asked to give fecal samples during the routine-surveillance visit (as per the normal clinical practice) at different: at baseline, after 6 months and after 12 months. Ospedale San Raffaele (OSR - Operative Unit (UO)1 (UO1)) is the promoter of this study. The other centers participating in the study are: * Ospedale Casa Sollievo della Sofferenza (CSS) - Foggia (UO2) * Azienda Ospedaliera San Camillo Forlanini - Roma (UO3) 150 subjects in total (100 patients with UC and 50 patients with T1D) will be enrolled at the IBD Center (Department of Gastroenterology and Digestive Endoscopy) and at the Pediatric Unit at Ospedale San Raffaele.