Grant: Team Grant: Health Challenges in Chronic Inflammation Initiative - (Full Appl)

The liver and gut forms an important partnership to digest, absorb and process harmless food particles (antigens). To perform this function successfully both organs need to be able to be tolerant of food antigens whilst retaining the ability to mount vigorous immune responses to ingested harmful bacteria and viruses (pathogens). Disruption of this balance with increased inflammation and reduced tolerance is at the root of most common gut and liver diseases. This includes conditions ranging from simple food intolerances to inflammatory bowel disease (IBD) and severe liver disease in the form of Primary Sclerosing Cholangitis (PSC). In some individuals, inflammation spreads from the liver and gut to include the joint and leads to long term disability and pain. The cause of all 3 diseases is hypothesized to be a combination of genetic susceptibility and environmental factors that triggers an overactive immune system. Recent work has demonstrated that inflammatory liver, gut and joint diseases are remarkably similar as they have shared genetic susceptibility genes and respond to similar biological therapies. Thus in this grant we aim to understand in detail how these diseases are linked genetically and define shared biological pathways and common environmental triggers of disease such as smoking, pollution and obesity. We will then link all this data with clinical disease features and responses to treatments to define genetic and biological markers that can be used to predict disease features, complications or responses to treatment to make the best possible care decision for each individual. The strength of this this proposal lies in our intend to call on the collective experience of experts in IBD, liver disease and joint inflammation to combine forces to accelerate knowledge of the factors that link these three organs to cause disease and how we can modify them to the benefit of patient care.