Fenugreek, gut microbiota, and resiliency to Western diet

胡芦巴、肠道微生物群和对西方饮食的适应能力

• 批准号: 10228695
• 负责人: Jacqueline M Stephens
• 金额: $ 37.02万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10228695
• 关键词: Adult; American; Bacteria; Bioinformatics; Biological; Blood; Botanicals; Cardiovascular Diseases; Clinical; Clinical Research; Complex; Computer Models; Dangerousness; Data; Diabetes Mellitus; Diet; Elements; Emotional; Environment; Equilibrium; Fatty acid glycerol esters; Female; Fiber; Formulation; Generations; Germ-Free; Health; Healthcare Systems; Homeostasis; Impairment; Individual; Industrialization; Intestines; Lead; Link; Mediating; Mediator of activation protein; Mental Depression; Metabolic; Metabolism; Metagenomics; Modernization; Mus; Obesity; Patients; Physiological; Phytochemical; Population; Production; Proteins; Role; Sampling; Seeds; Series; Serum; Shapes; Testing; Therapeutic; Translations; Trigonella foenum-graecum; Unhealthy Diet; Validation; base; bioinformatics tool; cohort; commensal bacteria; design; dietary; dietary control; dysbiosis; experimental study; gut bacteria; gut dysbiosis; gut microbiota; improved; in silico; male; metabolome; metabolomics; microbial; microbiome; microbiota; microbiota transplantation; mouse model; neurobehavioral; novel; novel strategies; preservation; prevent; resilience; response; social; validation studies; western diet

Fenugreek (Trigonella foenum-graecum) is used in many parts of the world for diabetes, cardiovascular disease, and depression. While the mechanism(s) of these actions is not known, it is becoming increasingly clear that gut microbiota are key players in homeostasis and also mediate true first-pass metabolism of dietary compounds. Furthermore, the high protein and fiber content of fenugreek seeds is particularly suited to modify intestinal bacteria and offset the dysbiotic effects of high fat/low fiber Western-style diets. Indeed, data from our lab shows that fenugreek significantly alters intestinal microbial populations, and reverses key Western diet- induced changes to gut microbiota. Based on these observations, we propose the following hypothesis: Fenugreek induces physiologic resiliency via changes to intestinal microbiota Our hypothesis is based on the ability of fenugreek to offset diet-induced gut dysbiosis, and on data showing that fenugreek-shaped microbiota can replicate selected effects of fenugreek. While these data support a role for gut bacteria in beneficial responses to fenugreek, key data are needed to confirm and identify mechanisms by which fenugreek-microbiota interactions drive physiologic benefits. First, the impact of gut microbiota on the beneficial profile of fenugreek needs to be established. Further, whether fenugreek-microbiota interactions alter the gut metabolome directly via unmasking/generation of otherwise-inaccessible botanical phytochemicals; or indirectly via altered metabolism of Western diets should be resolved. Finally, identification of intestinal and blood-based metabolites that mediate fenugreek-based physiologic resiliency is needed to accelerate the translation of these findings. To meet these needs, we have devised a unique experimental approach combining conventional and germ-free mice, an adaptive microbiome transplantation paradigm, and a series of cutting-edge in silico analyses to identify microbiome-derived, fenugreek-based metabolites that drive physiologic resiliency. Specific aim 1 conventionally-housed and germ-free mice to determine how intestinal microbiota shape the beneficial effects of fenugreek. Aim 2 will use microbiome transplants to determine if specific microbiota are both necessary and sufficient for the beneficial effects of fenugreek, and will determine if fenugreek-microbiota interactions alter the gut metabolome directly via unmasking/generation of otherwise- inaccessible botanical phytochemicals; or indirectly via altered metabolism of Western diets. Aim 3 will identify the exact metabolites in blood and intestinal fractions that predict neurobehavioral and metabolic impairment using validation cohorts and state-of-the art bioinformatic tools. Identification of these metabolites, and the commensal bacteria responsible for their production, could spearhead the formulation of safe and effective strategies to preserve health in the today's modern environment. Furthermore, improved understanding how gut microbiota balance the interactions of adverse and beneficial dietary elements could be harnessed to promote physiologic resilience in all patients regardless of diet.

胡芦巴（Trigonella foenum-graecum）在世界许多地方用于治疗糖尿病、心血管疾病 疾病和抑郁症。虽然这些作用的机制尚不清楚，但它正变得越来越多 明确肠道微生物群是体内平衡的关键参与者，并且还介导饮食的真正首过代谢 化合物。此外，胡芦巴种子的高蛋白质和纤维含量特别适合修饰 肠道细菌并抵消高脂肪/低纤维西式饮食的生态失调影响。事实上，我们的数据 实验室表明胡芦巴显着改变肠道微生物群，并逆转西方饮食的关键- 引起肠道微生物群的变化。基于这些观察，我们提出以下假设： 胡芦巴通过改变肠道微生物群诱导生理弹性 我们的假设是基于胡芦巴能够抵消饮食引起的肠道菌群失调的能力，并且数据显示 胡芦巴形状的微生物群可以复制胡芦巴的选定效果。虽然这些数据支持一个角色 对于肠道细菌对胡芦巴产生的有益反应，需要关键数据来确认和识别机制 胡芦巴与微生物群的相互作用可带来生理益处。首先，肠道菌群对肠道菌群的影响 需要确定胡芦巴的有益特征。此外，胡芦巴-微生物群相互作用是否会改变 通过揭示/生成其他方式无法获得的植物化学物质，直接影响肠道代谢组； 或者间接通过改变西方饮食的新陈代谢来解决。最后，鉴定肠道和 需要介导基于胡芦巴的生理弹性的血液代谢物来加速 这些发现的翻译。为了满足这些需求，我们设计了一种独特的实验方法 结合传统小鼠和无菌小鼠、适应性微生物组移植范例以及一系列 通过尖端的计算机分析来识别微生物组衍生的、基于胡芦巴的代谢物，这些代谢物驱动 生理弹性。具体目标 1 常规饲养且无菌的小鼠，以确定肠道如何 微生物群塑造了胡芦巴的有益作用。目标 2 将使用微生物组移植来确定是否 特定的微生物群对于胡芦巴的有益作用是必要且充分的，并将决定 如果胡芦巴-微生物群的相互作用通过揭露/产生其他物质直接改变肠道代谢组—— 难以获取的植物化学物质；或间接通过改变西方饮食的新陈代谢。目标 3 将确定 血液和肠道部分中预测神经行为和代谢损伤的确切代谢物 使用验证队列和最先进的生物信息学工具。这些代谢物的鉴定以及 负责其生产的共生细菌可以带头制定安全有效的 在当今现代环境中保持健康的策略。此外，加深了对如何 肠道微生物群平衡不利和有益饮食元素的相互作用，可用于 促进所有患者的生理恢复能力，无论饮食如何。