Ulcerative colitis (UC), one of several inflammatory bowel diseases (IBD), is a debilitating condition with no known cause and affects several million individuals in the US and Europe who require a lifetime of medication. Recently researchers have demonstrated that the types and quantities of bacteria in the gut define health status and that factors such as diet or host genotype may influence the composition of these microbial communities. More specifically, it has been demonstrated that certain types of bacteria in the GI tract of mice can induce inflammatory responses characteristically found in UC patients, suggesting that gut microbes play a large role in this disease.  This idea is supported by new studies showing that, compared to healthy people, UC patients have lost many of the bacteria normally present in the gut that presumably help maintain a balanced immune response.  Diet, particularly a Westernized diet high in animal fat and protein, is suspected to play a role in the development of inflammatory bowel disease. Support for this comes from studies that have demonstrated that the incidence of IBD is relatively low amongst Indians who reside in India and consume a native diet.  However, Asian migrants who adopt Western diets develop IBD at rates similar to, or even greater than, the local population.  Very recent data have indeed demonstrated that long-term diet habits are associated with specific types of bacteria in the gut, even in healthy individuals.  Hence, we propose that migrant UC patients, due to the adoption of a Western diet and genetic pre-disposition, develop a microbiota enriched for pro-inflammatory species, which contribute to UC development and severity of disease.  To examine this we will examine the GI microbes (bacterial, fungal, and viral species) of migrant UC patients, determine which organisms distinguish them from healthy subjects, and define the factors that influence microbiota composition.  In addition, we will examine ethnically distinct (European or South Asian) UC patients who exhibit distinct genotypes related to risk of UC development and determine whether the presence or absence of mutations in these genes is related to the types of bacteria in the lower GI tract. These studies attempt to define the types of microbes associated with UC, reveal factors that group distinct UC patients, and identify the specific microbial species (bacterial, fungal, and/or viral) correlated with this disease.  This study will lead to a much greater understanding of the role of microbes in UC and potentially provide information leading to development of novel therapeutics for this disease.