Multiomic Signatures of Microbial Metabolites Following Prebiotic Fiber Supplementation

摘要 富含酚类物质的益生元纤维与许多积极的健康结果相关，但它们 生物利用度通常较低。很大一部分肠道微生物群代谢这些纤维，释放出一系列的 酚酸，其被认为是驱动疾病风险降低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它们的代谢产物之间存在联系。 这些化合物发挥的下游生物效应。因此，我们建议召集一批 将接受益生元补充的个体，在全面的纵向表征期间， 微生物群和宿主变化的多组学分析（目的1）。然后我们将这些多组 数据（目标2），产生独特的生物特征，定义微生物代谢物的作用，从特定的 细菌在宿主的生物活动中发挥作用。然后我们将分离微生物菌株和相关的代谢产物 与宿主生物学活性，验证其在gnotobiotic小鼠中的功能，并合成新鉴定的 体外微生物分子，并展示其结构，生物学特性和应用（目标3）。 通过这项研究，我们希望能够详细而清晰地了解生理变化， 机制水平，发生在微生物组和宿主中，以响应膳食补充益生元 光纤

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.