Harnessing gut microbiota to reduce inflammation using broccoli-sprout diets

项目摘要 炎症性肠病(IBD)是一种知之甚少的胃肠道疾病。 以发炎为特征的。流行的理论是遗传和环境相结合 影响宿主免疫系统与肠道微生物区系相互作用的因素。我们的中心假设 食用特定的西兰花芽制剂会引起肠道微生物区系的变化 这不仅能促进抗炎生物活性物质的产生，还能促进肠道 动态平衡。我们的实验室表明，胃肠道有一种解剖模式， 西兰花芽衍生的生物活性水平很高，这与饮食诱导的肠道变化相对应 微生物群落。我们发现肠道微生物区系有助于非活动性细菌的转化。 生物活性的前体，以及特定的西兰花芽制剂改变其能力 生物转化，以及小鼠对结肠炎的易感性。然而，一个显著的知识差距 关于饮食生物活性物质改变疾病风险和作用的机制仍然存在 肠道微生物区系。我们的近期目标是确定西兰花发芽饮食的机制 影响小鼠对IBD的易感性。我们的长期目标是开发一种饮食制剂 对人类IBD有治疗作用的西兰花芽。我们的创新方法 使用不同的西兰花芽制剂来帮助区分肠道微生物区系和植物- 衍生的酶活性。我们使用了一系列“组学”方法来绘制空间地图 微生物群落和代谢物分布沿胃肠道变化，以更好地评估 西兰花发芽饮食引起的变化。我们用培养来补充“组学”方法， 并使用两个互补的战略研究模型来验证我们的研究设计。目标1 测试了一种解剖模式的假设，即胃肠道微生物区系转化西兰花 并帮助我们确定这种微生物生物转化是不是 对西兰花化合物的剂量敏感。我们将使用我们建立的DSS鼠标模型 探讨不同西兰花芽制剂对溃疡性结肠炎的影响 胃肠道微生物区系的浓度；由此产生的生物活性物质浓度 在肠道组织中；在小鼠结肠炎的发展上。AIM 2测试了使用 免疫抑制小鼠模型在饮食预防研究中提供了较强的 使用西兰花芽预防IBD的翻译策略。当暴露在 特定的细菌病原体，免疫抑制的小鼠发生慢性小肠结肠炎 类似于克罗恩氏病。这种以饮食为基础的方法为开发 改善IBD患者健康的可获得性和公平的战略。

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.