Preclinical Human IBD Mechanisms
Preclinical human IBD mechanisms is part of the five focus areas, including environmental triggers, novel technologies, precision medicine, and pragmatic clinical research, described in the Challenges in IBD Research document.
The focus of the Preclinical Human IBD mechanism studies is on research, directly relevant to IBD as experienced by patients. The main goal is to extrapolate from the laboratory studies of biochemical pathways, relevant to human IBD, using humanized disease models, to yield novel and effective therapeutic interventions. The specific research gaps include: 1) triggers of immune responses; 2) intestinal epithelial homeostasis and wound repair; 3) age-specific pathophysiology; 4) disease complications; 5) heterogeneous response to treatments; and 6) determination of disease location.
Read more about preclinical human IBD mechanisms in Inflammatory Bowel Diseases.
Currently, the Foundation is supporting three multi-institutional research initiatives aiming to understand the biological basis of human IBD: the Genetics Initiative, Microbiome Initiative, and Fibrosis Initiative. The goals and the impact of these initiatives are described below.
A collaborative initiative to study the contribution of genes to IBD and find gene-controlled pathways that may help in the design of new IBD medications.
These studies will lead to development of new therapeutic approaches that target genetically-controlled pathways in IBD.
A multi-institutional project to identify, compare, and analyze intestinal microbial populations and their metabolic byproducts, and the role they play in the origin and progression of IBD.
These studies may result in the development of microbiome-based interventions, such as therapeutic bacterial cocktails, that will allow patients to better manage and potentially treat IBD; or supplementation of bacterial metabolites with anti-inflammatory properties or capable of repairing the damaged intestinal wall.
A multi-disciplinary collaborative study investigating the biological mechanisms leading to the buildup of scar tissue in the gut of IBD patients, a phenomenon known as fibrosis. A sustained fibrosis process results in the formation of strictures (a narrowing of the intestinal passage), that in most cases requires surgery due to irreversible obstruction of the gut.
This project leverages from an extensive and well-annotated biobank of blood samples from IBD patients collected for over ten years. Using state of the art stem cell technology, these blood cells are now being converted into intestinal three-dimensional “mini-guts” grown in vitro, to generate the so-called “gut-in-a-dish” model system.
This unique humanized model system is being used to study the contribution of individual genes and intestinal microbes in driving the fibrosis process. This system can also be used to screen, identify, and test new drug candidates that could prevent or treat fibrosis.