Harnessing gut microbiota to reduce inflammation using broccoli-sprout diets

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Project Summary Inflammatory bowel disease (IBD) is a poorly understood gastrointestinal (GI) condition characterized by inflammation. The prevailing theory is that combined genetic and environmental factors disrupt the host immune system’s interaction with gut microbiota. Our central hypothesis is that consumption of specific broccoli sprout preparations elicits changes in the gut microbiota that not only improve the production of anti-inflammatory bioactives, but also promote intestinal homeostasis. Our labs have shown there is an anatomical pattern along the GI tract where broccoli sprout-derived bioactive levels are high which correspond to diet-induced changes in gut microbial communities. We showed that gut microbiota contribute to the transformation of inactive precursors to bioactives, and that specific broccoli sprout preparations alter their capacity for biotransformation, and the susceptibility of mice to colitis. However, a significant knowledge gap remains regarding the mechanisms by which dietary bioactives modify disease risk and the role of gut microbiota. Our immediate goal is to identify the mechanisms by which broccoli sprout diets affect susceptibility to IBD in mice. Our long-term goal is to develop a dietary preparation of broccoli sprouts which has therapeutic effects against IBD in humans. Our innovative approach uses different preparations of broccoli sprouts to help differentiate gut microbiota versus plant- derived enzymatic activities. We employ a combination of “omics” approaches to spatially-map the microbial community and metabolite profile changes along the GI tract, to better assess changes induced by broccoli sprout diets. We complement “omics” approaches with culturing, and validate our study design using two complementary models for strategic research. Aim 1 tests the hypothesis of an anatomical pattern where the GI tract microbiota transform broccoli compounds into bioactives, and helps us determine whether this microbial biotransformation is sensitive to dose of broccoli compounds. We will use our established DSS-mouse-model of ulcerative colitis to investigate the effects of different broccoli sprout preparations and concentrations on the microbiota along the GI tract; on the resulting concentration of bioactives in gut tissues; and on the development of colitis in mice. Aim 2 tests the benefits of using an immunosuppressed mouse model in the dietary prevention study to provide a stronger translational strategy for the use of broccoli sprouts for IBD prevention. When exposed to a specific bacterial pathogen, the immunosuppressed mice develop chronic enterocolitis resembling Crohn’s disease. This diet-based approach provides critical information for developing accessible and equitable strategies for improving health of IBD patients.