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，它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。直接从碳水化合物中提取的生物标志物是理想的。然而，在人们通常食用的特定食物的碳水化合物结构尚不清楚这一点上，存在着一个根本性的研究空白。长期目标是确定所有常见食物饮食摄入的特定聚糖生物标志物。本应用程序的目的是根据食物的单糖和连锁组成建立一个详细的碳水化合物结构文库，并评估碳水化合物结构作为饮食摄入生物标志物的效用。我们的中心假设是，特定食物具有独特的碳水化合物结构，可以作为饮食摄入量的生物标志物。这一假设是在初步研究的基础上提出的，其中：(a)已经确定了数百种食物的详细碳水化合物结构；(b)断奶婴儿食物的饮食干预导致粪便聚糖、微生物和代谢物的差异。人类肠道中的酶及其补体微生物对碳水化合物结构特征具有特异性。因此，我们的具体目标是：(1)利用食物和粪便配对分析平台构建糖聚糖文库；(2)利用生物反应器研究构建微生物基因标记文库；(3)检验糖聚糖和微生物生物标记物在人类摄食研究中的预测价值。该方法具有创新性，将前所未有的高分辨率碳水化合物含量分析——单糖和食物连锁分析——与多组学测量相结合，用于饮食摄入的生物标志物预测。这项研究具有重要意义和影响力，因为食物的高分辨率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，其中饮食是必不可少的组成部分。

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.