ANNA-THERESA D'HOOGHE (KU Leuven): Unlocking Precision Medicine in Inflammatory Bowel Diseases
Inflammatory bowel diseases (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC) are a heterogeneous entity, with a spectrum in disease severity and treatment responses. Current treatments achieve remission in only 30-40% of patients, leading to frequent drug changes and often surgery. A deeper molecular understanding of IBD's diverse phenotypes is crucial for better patient stratification and identifying new treatment targets, particularly for multi-refractory patients.
This project aims to unravel heterogeneity in UC severity by creating a detailed molecular map of UC patients with extreme phenotypes. We will leverage in-depth molecular transcriptomic, serum proteomic, whole-exome sequencing (WES) and spatial (subset) characterization of 150 patients with mild (in durable remission with 5-ASA only), responsive (in durable remission after first targeted therapy) and refractory (failed at least two targeted therapies) UC. Subsequently, multi-omic data integration will be performed to identify a prognostic classifier. Finally, we will validate this classifier in a longitudinal IBD inception cohort, assess its stability over time and investigate whether it can also be applied to colon-dominant Crohn’s disease.
In conclusion, our aim is to benchmark the UC heterogeneity severity spectrum and identify a composite biomarker with prognostic value. This project will help shape a new era of precision medicine in IBD, ensuring that patients receive the right treatment at the right time, based on their unique molecular profile. This would enhance patients' quality of life, minimize complications, and reduce healthcare costs.
EVA VISSERS (KU Leuven): The role of ultra-processed foods in the pathophysiology of inflammatory bowel diseases
Over the last decades, the prevalence of IBD, including Crohn’s disease and ulcerative colitis, has increased significantly worldwide. Epidemiological studies point to the increasing consumption ultra-processed foods (UPFs) as a possible contributing factor. UPFs typically contain non-nutritional components such as food additives and compounds formed during the industrial processes. Despite their extensive consumption, the effect of these UPF components on the intestinal environment remains poorly characterized.
Therefore, the aim of this research project is to elucidate the effect of UPF components on the intestinal microbiota, mucus layer, and epithelium to get a better understanding of how UPFs are involved in IBD.
To investigate this, intestinal microbiota from stool samples of patients with IBD will be combined with UPF components in a batch fermentation model. The change in microbial composition and production of metabolites will be evaluated. Next, intestinal organoid-derived monolayers from patients with IBD, which model the intestinal epithelium, will be exposed to the UPF components and the effects on permeability, mucus, and inflammation will be analyzed. Lastly, microbiota-driven effects on the epithelium will be assessed by exposing the organoid-derived monolayers to the supernatant of microbial fermentation.
Overall, the results of this study will provide further insights in the role of UPF components in the development and disease course of IBD and contribute more targeted dietary advices for patients.