Gastrointestinal Disease

Key areas of focus

  • Understand disease heterogeneity
  • Identify new treatment targets
  • Explore ‘environmental’ triggers of disease

The Gastrointestinal Disease theme aspires to transform our understanding, management and treatment of major intestinal and liver diseases. The disease areas we study are:

  1. The inflammatory bowel diseases Crohn’s disease and ulcerative colitis. These are chronic, life-long inflammatory conditions of the intestinal tract that are often first diagnosed in teenage years or in the 20s. The prevalence of these diseases has massively increased world-wide over the last decades, and the UK has one of the highest rates in the world, with an estimated 1 in 200 people affected.
  2. Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. These diseases are related to obesity and have massively increased. Indeed, one third of the UK population suffers from non-alcoholic fatty liver disease by now. A proportion of those patients will develop non-alcoholic steatohepatitis, the progressive form of fatty liver disease, which can lead to terminal liver disease and liver cirrhosis.
  3. The chronic liver diseases primary biliary cirrhosis and primary sclerosing cholangitis – these are rare, immune-mediated diseases that lack effective medical therapy and often require liver transplantation.
  4. Acute alcoholic hepatitis. This condition develops in a small subset of individuals consuming alcohol, but is particularly deadly. No effective therapy exists, and up to ~40% may die from liver failure within 6 months of diagnosis.

Research over the last decade has identified genes that put individuals at risk for developing any of these diseases. Inflammatory bowel disease and liver diseases have been amongst those most successfully studied for their genetic risk landscape. In contrast, ‘environmental factors’ that trigger disease in such genetically susceptible individuals remain largely unknown. This is one of the aspects we will address in this theme, to understand fundamental mechanisms of disease and investigate novel treatment targets. Of particular interest will be the contribution of diet and how the individual responds to it (e.g. hormonal regulation), as well as the microbial ecosystem (‘microbiota’) that inhabits our intestines and has a profound impact in disease.

Related to fundamental disease mechanisms is disease heterogeneity. This refers to the fact that different mechanisms may be at play in individual patients. In consequence, individual patients might require different therapies for their conditions (‘precision medicine’). Understanding disease heterogeneity and developing biomarkers to predict response is a major goal across the disease areas studied.

An important aspect of disease heterogeneity relates to prognosis. The establishment of biomarkers that predict prognosis is a further key goal, to allow selecting those patients that will benefit most from intensive therapy.

To achieve these goals, we will combine latest cutting-edge technology, experimental medicine, and disease modelling strategies with access to deeply clinically characterised patient populations, where individuals have been consented to be recalled to the Bioresource for specific investigations.