Project Summary

In this study we aim to:

1. Develop a novel treatment for IBD, using the recently described anti-inflammatory effects of the bile acid sensor farnesoid X receptor (FXR). We aim to develop agonists capable of selectively activating the FXR as a pharmaceutical lead.

2. Develop a non-invasive diagnostic tool using well-defined changes in the gut microbiome of people affected with IBD as a marker to diagnose and monitor disease progression or remission in stool samples.

In order to achieve these objectives we will develop 2 novel biological high-throughput screening assays (luciferase- and cofactor interaction-based) with which we can assay selective activity of FXR. These screening assays will be dictated by fundamental scientific insights in FXR-mediated activity and signal transduction. Meanwhile, a new non-invasive microbiome-based diagnostic tool will be generated and validated using feces from well-defined patients with IBD.

Ultimately, this project will culminate in proof of principle using first-in-men clinical trials to demonstrate that the anti-inflammatory activity of FXR agonists can be used to treat IBD successfully in vivo.

As illustrated above, the development of a new IBD-treatment option and the validation of a novel diagnostic tool require the input of several  domains of scientific knowledge, all present within this consortium, comprising of the UMC Utrecht (Depts Metabolic diseases and  Gastroenterology & Hepatology), TES Pharma and Enterome Biosciences.