Harnessing gut microbiota to reduce inflammation using broccoli-sprout diets

利用西兰花芽饮食利用肠道微生物群来减少炎症

• 批准号: 10514847
• 负责人: Suzanne Ishaq Pellegrini
• 金额: $ 43.6万
• 依托单位: UNIVERSITY OF MAINE ORONO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10514847
• 关键词: Affect; Anatomy; Anti-Inflammatory Agents; Bacteria; Biomedical Research; Broccoli - dietary; Chronic; Clinical; Colitis; Complement; Consumption; Crohn' s disease; Development; Diet; Dietary Component; Disease; Disease Outcome; Disease Progression; Dose; Enterocolitis; Environmental Risk Factor; Enzymes; Epithelial; Exposure to; Functional disorder; Future; Gastrointestinal tract structure; Genetic; Glucosinolates; Goals; Health; Human; Immune response; Immune system; Immunological Models; Inflammation; Inflammatory Bowel Diseases; Interleukin-10; Isothiocyanates; Knowledge; Location; Maps; Metabolic Biotransformation; Modeling; Morphology; Mus; Myrosinase; Pathology; Patients; Pattern; Plants; Predisposition; Preparation; Prevention; Production; Quality of life; Research; Research Design; Research Personnel; Resolution; Role; Source; Sulforaphane; System; Testing; Therapeutic Effect; Tissues; Translations; Ulcerative Colitis; absorption; base; career; cruciferous vegetable; dextran sulfate sodium induced colitis; dietary; disorder prevention; disorder risk; fecal microbiota; gastrointestinal; glucoraphanin; gut microbiota; immunosuppressed; improved; in vivo Model; innovation; intestinal homeostasis; microbial; microbial community; microbiome; microbiota; mouse model; pathogenic bacteria; protective effect; research and development; theories; translational approach; undergraduate student

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.

项目摘要 炎症性肠病（IBD）是一种知识渊博的胃肠道（GI）条件 以炎症为特征。普遍的理论是结合遗传和环境 因素破坏了宿主免疫系统与肠道菌群的相互作用。我们的中心假设 是否消耗特定的西兰花发芽制剂会引起肠道菌群的变化 这不仅改善了抗炎生物活性剂的产生，而且还可以促进肠道 稳态。我们的实验室表明，沿着胃肠道有一个解剖模式 西兰花发芽衍生的生物活性水平很高，对应于饮食引起的肠道变化 微生物社区。我们表明肠道菌群有助于不活跃的转化 生物活性剂的前体，而特定的西兰花发芽制剂改变了其能力 生物转化以及小鼠对结肠炎的敏感性。但是，一个很大的知识差距 仍然涉及饮食生物活性改变疾病风险和作用的机制 肠道微生物群。我们的近期目标是确定西兰花芽饮食的机制 影响小鼠对IBD的敏感性。我们的长期目标是制定饮食准备 西兰花新芽对人类具有治疗作用。我们的创新方法 使用不同的西兰花豆芽制剂来帮助区分肠道菌群与植物 - 衍生的酶活性。我们采用了“ OMICS”方法的结合来进行空间映射 微生物群落和代谢物谱沿胃肠道变化，以更好地评估 西兰花发芽饮食引起的变化。我们与文化相辅相成的方法， 并使用两个完整的战略研究模型来验证我们的研究设计。目标1 测试胃肠道菌群转化西兰花的解剖模式的假设 化合物成生物活性剂，并帮助我们确定这种微生物生物转化是否是 对西兰花化合物的剂量敏感。我们将使用我们已建立的DSS鼠标模型 溃疡性结肠炎研究不同的西兰花发芽制剂的影响 沿着胃肠道的微生物群的浓度；生物活性剂的浓度 在肠道组织中；以及小鼠结肠炎的发展。 AIM 2测试使用 在饮食预防研究中，免疫抑制的小鼠模型可提供更强的 使用西兰花新芽进行IBD预防的翻译策略。当暴露于 特定细菌病原体，免疫抑制小鼠发生慢性小肠结肠炎 类似于克罗恩病。这种基于饮食的方法为开发提供了关键信息 可访问且公平的策略，以改善IBD患者的健康状况。

项目成果

Early life exposure to broccoli sprouts confers stronger protection against enterocolitis development in an immunological mouse model of inflammatory bowel disease.

在炎症性肠病的免疫小鼠模型中，生命早期接触西兰花芽可以提供更强的保护，防止小肠结肠炎的发展。

• DOI: 10.1101/2023.01.27.525953
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Holcomb,Lola;Holman,JohannaM;Hurd,Molly;Lavoie,Brigitte;Colucci,Louisa;Hunt,Benjamin;Hunt,Timothy;Kinney,Marissa;Pathak,Jahnavi;Mawe,GaryM;Moses,PeterL;Perry,Emma;Stratigakis,Allesandra;Zhang,Tao;Chen,Grace;Ishaq,Suzanne
• 通讯作者: Ishaq,Suzanne