Professor Holm Uhlig is based at the Translational Gastroenterology Unit and studies defects in the immune response and regulation leading to immunopathology. Dr Uhlig is interested in children with inflammatory bowel disease, and aims to understand the complex puzzle of molecular mechanisms involved.
The gastrointestinal tract is home to more bacteria than there are cells in our body. Our immune system needs to maintain a strong and effective immune response towards pathogenic bacteria, whilst maintaining tolerance towards commensal bacteria that have a function within the gut. A better understanding of these mechanisms can improve our treatment options.
Research in Medicine needs to ultimately translate into better treatment of patients. Researchers at the Nuffield Department of Medicine, University of Oxford, collaborate to develop better care and improved preventive measures. Findings in the laboratory are translated into changes in clinical practice, from Bench to Bedside.
Q: What is the challenge of the immune system in our gastrointestinal tract?
HU: The gastrointestinal tract harbours a tremendous amount of bacteria; in fact there are tenfold more bacteria in the gastrointestinal tract than there are cells in our body. In addition to these viruses there are fungi and parasites, and the task of the immune system is to maintain a very strong and effective immune response towards pathogenic bacteria that can invade the body, that can cause tissue damage, whilst maintain tolerance towards the majority of those bacteria within the gut that we call commensal that have a function within the gut, within metabolism and that have evolved with us during evolution.
Q: What happens when these mechanisms don’t work anymore?
HU: There are several possibilities that this can happen. There could be a change in the composition of the bacterial flora, there can be change in the epithelial lining disturbing the integrity of the epithelium, there can be defects in the defence mechanisms of our immune cells, or it could be a breakdown of the tolerance and the mechanisms that maintain a stable immune homeostasis. And that could all lead to an increased load of bacteria entering the body and leading to an increased immune response ultimately leading to tissue destruction.
Q: Does this affect children as well as adults?
HU: Indeed it does. There are diseases called Inflammatory Bowel Disease, which in comprises two major groups called Crohn's Disease and Ulcerative Colitis, and about one fifth of patients with Inflammatory Bowel Disease have first symptoms during childhood or adolescence.
Q: What are the most important lines of research that have been developed over the last five to ten years?
HU: I think there has been a tremendous revolution both in immunology and in genetics, and combining these two areas is a really exciting field. The changes in the genetics now allow both to investigate the genome of humans to find genetic defects - that would be to look for the needle in the haystack that could be responsible for changes in our immune response towards bacteria. On the other hand it allows us to look for the composition of the bacterial flora and really to analyse a lot of bacteria that have never been cultured before.
Q: Why does your line of research matter, why should we put money into it?
HU: We think that we can improve treatment for patients. There is a burden of disease for these patients; they require surgery, they require treatment with immunosupressors or anti inflammatory medication, and if we can understand the immune system and how to deal with the increased inflammatory response, if we can understand the immunodeficiency that goes along with some of those diseases then we can improve our treatment options.
Q: How does your research fit into translational medicine within the department?
HU: The Translational Gastroenterology Unit headed by Fiona Powrie tries to be an umbrella for several investigators as well as research groups. There are basic scientists, biologists, biochemists trying to understand protein function, protein-protein interactions, trying to understand cell-cell interactions at the lab bench, and this spans to translational efforts trying to use these mechanisms at the bedside and trying to introduce new treatment options in clinical trials within the department.