Harnessing gut microbes for glycan detection and quantification

Abstract 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 will inform new therapeutic avenues to treat diseases via modulation of the gut microbiota composition and metabolism. However, examining heterogenous 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. We have harnessed this microbial machinery to indicate the presence and abundance of compositionally similar, yet structurally distinct glycans, using a newly developed transcriptional reporter. We demonstrate how these tools can be implemented to examine glycan mixtures, isolate target molecules for downstream characterization, and quantify the recovered products. We assert that this new toolkit will dramatically enhance our understanding of the mammalian intestinal environment and identify host-microbial interactions critical for human health.