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）是一种了解甚少的胃肠道（GI）疾病 以发炎为特点。流行的理论是，结合遗传和环境 这些因素破坏了宿主免疫系统与肠道微生物群的相互作用。我们的核心假设 食用特定的西兰花芽制品会导致肠道微生物群的变化， 这不仅可以提高抗炎生物活性物质的生产，还可以促进肠道 体内平衡我们的实验室显示胃肠道沿着有一种解剖模式 西兰花芽衍生的生物活性水平高，这对应于饮食诱导的肠道变化， 微生物群落我们发现，肠道微生物群有助于将非活性的 前体的生物活性物质，以及特定的西兰花芽制剂改变其能力， 生物转化和小鼠对结肠炎的易感性。然而，一个重大的知识差距 关于饮食生物活性物质改变疾病风险的机制以及 肠道菌群的数量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膳食制剂， 西兰花芽对人体IBD有治疗作用。我们的创新方法 使用不同的西兰花芽来帮助区分肠道微生物群和植物， 衍生酶活性。我们采用“组学”方法的组合， 微生物群落和代谢产物谱沿着胃肠道变化，以更好地评估 西兰花芽饲料引起的变化。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验证我们的研究设计。要求1 检验了胃肠道微生物群转化西兰花的解剖模式的假设， 化合物转化为生物活性物质，并帮助我们确定这种微生物的生物转化是否 对西兰花化合物的剂量敏感。我们将使用我们建立的DSS小鼠模型， 溃疡性结肠炎，以研究不同的西兰花芽制剂和 在沿着胃肠道沿着的微生物群上的浓度;在生物活性物质的所得浓度上 在肠道组织中;以及对小鼠结肠炎的发展。目标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更强的 西兰花芽用于IBD预防的翻译策略。当暴露于 特定的细菌病原体，免疫抑制小鼠发展为慢性小肠结肠炎 类似克罗恩病这种以饮食为基础的方法为开发 改善IBD患者健康的可及且公平的策略。

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