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We aim to characterise markers of liver function, intestinal inflammation and microbial metabolism over time in a cohort of patients with primary sclerosing cholangitis (PSC) and/or ulcerative colitis (UC). This will enable us to determine the dynamic nature of disease progression and correlations between liver and intestinal function and how these may influence the microbiome and disease outcomes.

Longitudinal Dynamics of the Hepatic-Intestinal axis in primary sclerosing cholangitis

overview of the study

We are collecting biological measurements in a cohort of patients with primary sclerosing cholangitis (PSC) and/or ulcerative colitis (UC). We will be taking measurements of liver function from blood tests, gut inflammation from faecal samples and bacterial metabolites also from faecal samples. These measures will be taken over time from patients with PSC that has not progressed to cirrhosis, allowing us to determine how the liver, the gut microbiome and gut tissue are changing over the course of 1 year.

 

A schematic figure showing lines that move along the x-axis that represents time. The figure represents potential changes in liver and gut inflammation across time.

why are we conducting this research?

Patients with PSC are very likely to also have inflammatory bowel disease (IBD). However, we don't yet understand the complex interaction between the liver, the instestine and the intestinal microbes (microbiome) in the development of PSC-IBD. However, the liver and the intestine communicate in very complex ways. For example, products that flow in the bile from the liver impact on nutrient absoription, can be modified by bacteria, and act as signaling molecules to affect immunity. We would like to find out more about these interactions and hope to be able to find out how periods of inflammation in the intestine alter what the bacteria are doing in the intestine and how this relates to liver function. A summary schematic diagram showing the liver and the intestine. Arrows are drawn from the liver to the intestine to represent the flow of bile acids and other molecules. Arrows are drawn from the intestine to the liver to show the flow of metabolites from the intestine to the liver.

the team

To conduct this research takes a team of people in order to enrol participants, collect biological samples, process samples and analyse data. The team members are listed below:

Nicholas Ilott: Researcher at the Kennedy Institute of Rheumatology.

Kate Coldwell: Daphne Jackson Trust Fellow at the Kennedy Institute of Rheumatology.

Isaac Dennis: Laboratory technician for the Oxford Centre for Microbiome research.

Claire Pearson: Lab manager and researcher at the Kennedy Institute of Rheumatology.

Emma Culver: Consultant Hepatologist & Senior Lecturer in Gastroenterology & Hepatology.

Arran Babbs: Clinical trials facility manager, gastroenterology and hepatology.

Lou Holland: Biobanker and Senior Clinical Trials Assistant.

Abbey Martin: Hepatology research nurse.

Denise O'Donnell: Clinical research operations manager.

James Chivenga: IBD cohort and database manager.

Chik On Choy: Scientific project manager for the Oxford Centre for Microbiome Studies.

Fiona Powrie: Professor of Musculoskeletal Sciences and Director of the Kennedy Institute.

Paul Klenerman: Sidney Truelove Professor of Gastroenterology.

James McCullagh: Professor of biological chemistry and director of the mass spectrometry research facility.

Simon Leedham: Wellcome Senior Research Fellow in Clinical Science and an Honorary Consultant Gastroenterologist

funding

This project is supported by an Early Career Development award from GutsUK. For more information on the work that GutsUK do and the research they fund visit their website.

gutsuk