Dietary fat effects on gut microbes, host immune state and experimental colitis

膳食脂肪对肠道微生物、宿主免疫状态和实验性结肠炎的影响

基本信息

批准号：
8890155
负责人：
EUGENE B CHANG
金额：
$ 46.28万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-25 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8890155
关键词：
Acids Affect Animals Antigen-Antibody Complex Base Composition Bioinformatics Biological Availability Clinical Trials Colitis Conjugated Linoleic Acids Crohn&apos s disease DNA Sequence Data Deltaproteobacteria Development Diet Dietary Fats Dietary Fatty Acid Dietary Intervention Dietary Supplementation Disease Disease Outcome Disease remission Enteral Environment Equilibrium Experimental Models Exposure to Fatty Acids Fatty acid glycerol esters Fish Oils Future Gene Targeting Genes Genetic Genetic Drift Genetic Predisposition to Disease Gnotobiotic Health Homeostasis Human Immune Immune response Incidence Individual Inflammation Inflammatory Bowel Diseases Inflammatory disease of the intestine Interleukin-10 Intestines Knowledge Lead Life Style Measures Mediating Microbe Milk Modeling Mus Outcome Patients Production Resistance Risk Role Safflower Oil Services Severities Smoking Solutions Source Staging Starch Structure Supplementation T-Lymphocyte Technology Testing Therapeutic Ulcerative Colitis Variant Volatile Fatty Acids base clinical application commensal microbes dietary supplements disease natural history disorder risk immunogenic immunogenicity improved insight intervention effect lard microbial microbiome next generation non-genetic novel strategies prevent saturated fat western diet

项目摘要

DESCRIPTION (provided by applicant): The unfortunate combination of genetic background and colonization by certain inciting commensal bacteria, can result in the development of inflammatory bowel diseases (IBD) in genetically susceptible individuals. Because little can be done presently to correct genetic susceptibility, changing the gut flora of IBD patients in a predictable and sustainable way represents a tangible and practical solution. We believe this can be accomplished through dietary manipulation of the enteric microbiota. Two hypotheses will be tested: (1) that certain dietary fats which that are well represented in "Western diets" ar capable of either precipitating or preventing/ameliorating colonic inflammation through their actions on the enteric microbiome (Aim 1), and (2) that dietary intervention with fatty acid supplements or increased short chain fatty acid bioavailability can reshape disease-causing enteric microbiomes to reduce risk or ameliorate IBD, thus setting the stage for future clinical application. We show, for instance, that risk for developing colitis in IL-10 KO mice can be significantly increased by diets high in saturated, milk-derived fat, which promote the bloom of immunogenic Deltaproteobacteria that are part of the "rare biosphere" of the enteric microbiome. We also show that several forms of dietary supplementation can reshape and alter the immunogenicity of saturated fat-induced changes in the enteric microbiota. These studies will take advantage of cultivation-dependent and -independent approaches and the bioinformatic analysis services of DDRCC Host-Microbe Core. In addition, microbiota transfer and gnotobiotic animal technologies will be used to determine if there is causal role of diet-induced changes of the enteric microbiota in creating immune imbalances and adverse risk outcomes. In summary, we will determine how diet affects and can be used to manipulate the enteric microbiota to restore immune homeostasis and reduce risk and severity of complex immune-mediated disorders. The knowledge gained through these studies will provide fundamental insights into the cause of IBD and help define dietary strategies to prevent or ameliorate IBD through manipulation of the enteric microbiota.

描述（由申请人提供）：通过某些煽动共生细菌的遗传背景和定殖的不幸结合可能会导致遗传易感人群的炎症性肠病（IBD）的发展。由于目前几乎无法做到以纠正遗传易感性，因此以可预测且可持续的方式改变IBD患者的肠道菌群代表了一种有形且实用的解决方案。我们认为，这可以通过对肠菌群的饮食操纵来实现。将测试两种假设：（1）在“西方饮食”中很好地代表的某些饮食脂肪能够通过对肠性微生物组的作用来沉淀或预防/改善结肠炎症（AIM 1），以及（2）用脂肪酸补充或增加脂肪酸的饮食中的饮食中的脂肪酸味或增加的脂肪酸味，可以使脂肪酸化或促进脂肪酸化可重新使用，并使酸性疾病的疾病均可促进脂肪酸性疾病，使得酸性疾病均可用来促进脂肪酸性疾病，使得酸性疾病的疾病可促进脂肪酸性疾病，使得酸性疾病均可促进脂肪酸性疾病。 IBD，因此为将来的临床应用奠定了基础。例如，我们表明，在饱和，牛奶来源的脂肪中，饮食中的饮食高显着增加了在IL-10 KO小鼠中发展结肠炎的风险，从而促进了肠性微生物组“稀有生物圈”的一部分免疫原性deltaproteobacteria。我们还表明，饮食补充的几种形式可以重塑和改变饱和脂肪诱导的肠菌群变化的免疫原性。这些研究将利用DDRCC宿主 - 微生物核心的培养依赖性和独立的方法以及生物信息学分析服务。此外，将使用微生物群转移和gnotobiotic动物技术来确定饮食诱导的肠性微生物群在产生免疫失衡和不良风险结果方面是否存在因果作用。总而言之，我们将确定饮食如何影响并可以用来操纵肠菌群以恢复免疫稳态并降低复杂免疫介导的疾病的风险和严重程度。通过这些研究获得的知识将提供对IBD原因的基本见解，并有助于通过操纵肠道微生物群来预防或改善IBD的饮食策略。