Department of Biochemistry & Molecular Biology, Penn State College of Medicine, Hershey, PA, 17033, USA.
Penn State Microbiome Center, The Pennsylvania State University, State College, PA, 16802, USA.
Nat Commun. 2023 Jan 17;14(1):275. doi: 10.1038/s41467-022-35626-2.
Glycans facilitate critical biological functions and control the mammalian gut microbiota composition by supplying differentially accessible nutrients to distinct microbial subsets. Therefore, identifying unique glycan substrates that support defined microbial populations could inform therapeutic avenues to treat diseases via modulation of the gut microbiota composition and metabolism. However, examining heterogeneous glycan mixtures for individual microbial substrates is hindered by glycan structural complexity and diversity, which presents substantial challenges to glycomics approaches. Fortuitously, gut microbes encode specialized sensor proteins that recognize unique glycan structures and in-turn activate predictable, specific, and dynamic transcriptional responses. Here, we harness this microbial machinery to indicate the presence and abundance of compositionally similar, yet structurally distinct glycans, using a transcriptional reporter we develop. We implement these tools to examine glycan mixtures, isolate target molecules for downstream characterization, and quantify the recovered products. We assert that this toolkit could dramatically enhance our understanding of the mammalian intestinal environment and identify host-microbial interactions critical for human health.
糖链通过为不同的微生物亚群提供不同的可利用营养物质，促进关键的生物学功能，并控制哺乳动物肠道微生物群落组成。因此，鉴定支持特定微生物群的独特糖链底物，可以为通过调节肠道微生物群落组成和代谢来治疗疾病提供治疗途径。然而，由于糖链结构的复杂性和多样性，对个体微生物底物的异质糖链混合物进行检查受到了阻碍，这给糖组学方法带来了巨大的挑战。幸运的是，肠道微生物编码专门的传感器蛋白，这些蛋白可以识别独特的糖链结构，并依次激活可预测的、特定的和动态的转录反应。在这里，我们利用这种微生物机制，使用我们开发的转录报告基因来指示组成相似但结构不同的糖链的存在和丰度。我们实施这些工具来检查糖链混合物，分离下游特征分析的目标分子，并定量回收产物。我们断言，这个工具包可以极大地提高我们对哺乳动物肠道环境的理解，并确定对人类健康至关重要的宿主-微生物相互作用。
