Multiomic Signatures of Microbial Metabolites Following Prebiotic Fiber Supplementation

摘要 富含酚类的益生菌纤维与许多积极的健康结果相关，然而他们的 生物利用度通常很低。很大一部分肠道微生物群代谢这些纤维，释放出一系列 酚酸被认为是降低疾病风险的主要生物活性成分。 尽管如此，几乎没有证据表明特定的肠道细菌与它们产生的代谢物和 这些化合物所产生的下游生物效应。因此，我们建议召集一批 在全面的纵向鉴定过程中，将接受益生素补充的个体 微生物区系和寄主的变化与多重组学分析(目标1)。然后我们将整合这些复合体 数据(目标2)，生成独特的生物签名，定义特定微生物代谢物的作用 细菌在宿主的生物学活动中发挥作用。然后我们将分离相关的微生物菌株和代谢物 通过宿主生物活性，验证它们在诺生菌小鼠中的功能，并合成新鉴定的 微生物分子的体外培养，并展示其结构、生物学特性和应用(目标3)。 通过这项研究，我们希望对生理变化有一个详细和清楚的了解，在 机械性水平，发生在微生物群和宿主中，以响应饲料中添加益生元 纤维。

ABSTRACT Phenolics-rich prebiotic fiber has been correlated with a number of positive health outcomes, however their bioavailability is typically low. A large portion the gut microbiota metabolize these fibers releasing a range of phenolic acids, which are believed to be principle bioactive components driving reduction in disease risk. Despite this, little evidence exists linking specific gut bacteria with the metabolites they produce and the downstream biological effects that these compounds exert. We therefore propose to assemble a cohort of individuals that will receive prebiotic supplementation, during comprehensive, longitudinal characterization of the microbiota and host changes with multiple omics assays (Aim 1). We will then integrate these multiomic data (Aim 2), generating unique biological signatures that define the role microbial metabolites from specific bacteria play in host biological activity. We will then isolate the microbial strains and metabolites associated with host biological activity, validate their function in gnotobiotic mice and synthesize the newly identified microbial molecules in vitro and demonstrate their structure, biological properties and applications (Aim 3). Through this study we expect to gain a detailed and clear understanding of the physiological changes, at the mechanistic level, that occur in the microbiome and host in response to dietary supplementation with prebiotic fiber.