Annotating carbohydrate structures to develop markers for consumption of food

食物消耗的生物标记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。直接来自碳水化合物的生物标记物是理想的。然而，有一个基本的研究空白，那就是通常消费的特定食物的碳水化合物结构是未知的。长期目标是确定所有常见食物的饮食摄入量的特定多糖生物标记物。目前应用的目的是根据食物的单糖和连接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膳食摄入量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，可以作为饮食摄入量的生物标志物。这一假设是在初步研究的基础上提出的，在这些研究中，(A)已确定数百种食物的详细碳水化合物结构，(B)粪便多糖、微生物和代谢物因婴儿断奶食物的饮食干预而不同。人类肠道中的酶及其补充微生物是碳水化合物结构特征所特有的。因此，本研究的具体目标是：(1)构建食品和粪便的配对分析平台的糖链文库；(2)利用生物反应器研究建立微生物基因标记库；(3)测试糖链和微生物生物标记物在人类喂养研究中的预测价值。这种方法是创新的，带来了前所未有的高分辨率碳水化合物含量分析--食物的单糖和连锁分析--结合多个基因组测量来预测饮食摄入量的生物标记物。这项拟议的研究意义重大，影响深远，因为一个高分辨率的食品聚糖库以及这些食品的糖-微生物生物标记物产品将改变未来的临床试验，在这些试验中，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.