Microbiome and immune regulation

Our vision: "driving excellence in medical research to build a healthier future" Our research centres on an exciting development in medical research for the prevention of inflammatory and autoimmune diseases. Here we investigate how diet and gut microbiota affects our immune system and modulate the course of inflammatory responses. Our research offers a scope to prevent or treat diabetes, obesity and diabetes complications such as kidney disease by using completely novel approaches, such as intervention with dietary and bacterial metabolites. Compelling evidence now supports the notion that diet and our own gut microbiota underpin many inflammatory diseases, including type 1 diabetes. Indeed this new advance now opens exciting new opportunities to prevent and/or treat diabetes and its complications by studying microbial metabolites. Our research crosses cutting-edge disciplines by connecting immunology, microbiology, metagenomics, metabolomics, and nutrition, which allow us to determine the role of gut digesta scfas-metabolites in the development of diabetes and the overcome of related complications. Type 1 diabetes is a t cell-mediated autoimmune disease resulting in the destruction of insulin-producing beta-cells in the pancreas. T1d has a strong genetic basis in humans and in mice. However, the environment is a significant contributor to innate immune inflammation. One of many candidate environmental factors is diet, which operates in a variety of ways ranging by affecting immune regulation and tolerance and promoting autoimmunity, from the delivery of excess energy leading to obesity and insulin resistance. Our work has demonstrated that high fibre diet protects NOD mice from diabetes in a process dependent on marked changes in regulatory t cells and other cell types central to t1d pathogenesis, consistent with an anti-inflammatory gut flora. We are seeking to understand the interactions between the gut microbiota directly with our immune system. Therefore, there is a potential to dramatically alter disease incidence through the identification of environmental influences, and the pathways they affect. As the head of the immunology and diabetes laboratory together with my group, we are focused on a new approach- the use of dietary metabolites to manipulate immune tolerance, gut homeostasis, and epigenetic changes to prevent autoimmune diabetes and moderate the risk of diabetes-related complications. Nutrition and microbial metabolites in inflammation The notion that diet and/or the gut microflora influences immunity and autoimmunity have not been taken in deep consideration, in part because precise molecular pathways had not been identified. Our group has demonstrated that short-chain fatty acid, which are produced by gut bacteria during fiber fermentation or digestion have anti-inflammatory effects. Autoimmune diabetes associates with ‘western lifestyle' and incidence in children has been increasing by ~3% per year, indicative of an environmental influence. We believe diet and bacterial metabolites may represent an effective, non-pharmacological means to modulate gut and immune homeostasis to prevent autoimmune diabetes.