Fenugreek, gut microbiota, and resiliency to Western diet

胡芦巴（Trigonella foeti-graecum）在世界上许多地方用于糖尿病、心血管疾病和糖尿病。 疾病和抑郁症。虽然这些行动的机制尚不清楚，但它正变得越来越重要。 很明显，肠道微生物群是体内平衡的关键参与者，也介导了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于改性。 这类食物能有效地抑制肠道细菌，并抵消高脂肪/低纤维西式饮食的生态失调效应。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种群，并逆转关键的西方饮食- 引起肠道菌群的变化。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抵消饮食引起的肠道生态失调的能力， 胡芦巴形状的微生物群可以复制胡芦巴的特定效果。虽然这些数据支持一个角色， 对于肠道细菌对胡芦巴的有益反应，需要关键数据来确认和确定机制 胡芦巴-微生物群相互作用驱动生理益处。首先，肠道微生物群对 需要确定胡芦巴的有益特性。此外，胡芦巴-微生物群的相互作用是否会改变 肠道代谢组直接通过揭露/生成否则难以获得的植物化学物质; 或间接通过改变西方饮食的代谢应该得到解决。最后，确定肠和 需要介导胡芦巴生理弹性的血液代谢物来加速 翻译这些发现。为了满足这些需求，我们设计了一种独特的实验方法 结合常规和无菌小鼠，适应性微生物组移植范例，以及一系列 尖端的计算机分析，以确定微生物组衍生的，基于胡芦巴的代谢物， 生理弹性具体目标1常规饲养和无菌小鼠，以确定肠道 微生物群塑造了胡芦巴的有益效果。Aim 2将使用微生物组移植来确定 特定的微生物群对于胡芦巴的有益效果是必要的和足够的，并将决定 如果胡芦巴-微生物群的相互作用通过暴露/产生其他- 难以接近的植物化学物质;或间接通过改变西方饮食的新陈代谢。目标3将确定 预测神经行为和代谢障碍的血液和肠道成分中的确切代谢物 使用验证队列和最先进的生物信息学工具。鉴定这些代谢物， 负责其生产的益生菌，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，更好地了解如何 肠道微生物群平衡不利和有益的饮食元素的相互作用可以被利用， 促进所有患者的生理恢复力，无论饮食如何。

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.