Annotating carbohydrate structures to develop markers for consumption of food

食物消耗的生物标志物是临床和喂养研究的重要指标，这些研究建立了我们对营养的理解。碳水化合物是健康饮食的最大组成部分。直接来源于碳水化合物的生物标志物是理想的。然而，存在一个基础研究空白，因为人们通常食用的特定食物的碳水化合物结构尚不清楚。长期目标是确定所有常用食物的膳食摄入量的特定聚糖生物标志物。本申请的目的是根据其单糖和连接组成开发食物的详细碳水化合物结构库，并评估碳水化合物结构作为膳食摄入的生物标志物的效用。我们的中心假设是特定的食物具有独特的碳水化合物结构，可以作为饮食摄入的生物标志物。这一假设是基于初步研究提出的，其中（a）已经确定了数百种食物的详细碳水化合物结构，（B）婴儿断奶食物的饮食干预导致粪便聚糖、微生物和代谢物不同。来自人类及其补体微生物的肠道中的酶对结构碳水化合物特征具有特异性。因此，具体目标是（1）构建具有食物和粪便配对分析平台的糖组学文库，（2）使用生物反应器研究进行微生物基因标志物文库，以及（3）在人类喂养研究中检测聚糖和微生物生物标志物的预测价值。该方法是创新的，带来了前所未有的高分辨率碳水化合物含量分析-单糖和食物的连锁分析-与多个组学测量，以生物标志物预测饮食摄入量。这项拟议的研究意义重大，影响深远，因为高分辨率的食物聚糖库以及这些食物的聚糖微生物生物标志物产品将改变未来的临床试验，其中饮食是一个重要组成部分。

Biomarkers of food consumption are important indicators for clinical and feeding studies that establish our understanding of nutrition. Carbohydrates make up the largest component of a healthy diet. Biomarkers that are derived directly from carbohydrates are ideal. However, there is a fundamental research gap in that carbohydrate structures of specific foods that are commonly consumed are unknown. The long-term goal is to determine specific glycan biomarkers of dietary intake for all commonly consumed foods. The objective of the current application is to develop a detailed carbohydrate structure library of foods in terms of their monosaccharide and linkage compositions and to evaluate carbohydrate structures for their utility as biomarkers of dietary intake. Our central hypothesis is specific foods have unique carbohydrate structures that can serve as biomarkers of dietary intake. This hypothesis has been formulated on the basis of preliminary studies in which (a) detailed carbohydrate structures have been determined for hundreds of foods and (b) fecal glycans, microbes, and metabolites differed by dietary intervention of weaning foods in infants. Enzymes in the gut from human and their complement microbes are specific to structural carbohydrate features. Therefore, the specific aims are to (1) construct a glycomic library with paired analytical platform for food and feces, (2) conduct a microbial gene marker library using bioreactor studies and (3) test the predictive value of glycan and microbial biomarkers in a human feeding study. The approach is innovative, bringing unprecedented high-resolution carbohydrate content analysis—monosaccharide and linkage analysis of foods—with multiple omic measurements to biomarker prediction of dietary intake. The proposed research is significant and impactful because a high-resolution glycan library of foods together with glycan-microbe biomarker products of those foods will transform future clinical trials in which diet is an essential component.