Harnessing gut microbes for glycan detection and quantification

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. Detecting distinct glycans within heterogeneous mixtures is hindered by glycan structural complexity and diversity. Here the authors exploit the ability of gut microbes to sense different glycan structures in order to develop quantitative glycan biosensors by coupling bacterial detection machinery to an optimised luciferase reporter.

Automated summary

The presence of distinct glycans in heterogeneous mixtures is challenging to detect due to structural complexity and diversity. In this study, the authors exploit the sensing abilities of gut microbes to develop quantitative glycan biosensors. They couple the bacterial detection machinery with an optimized luciferase reporter to indicate the presence and abundance of compositionally similar, yet structurally distinct glycans. These tools can greatly enhance our understanding of the mammalian gut environment and identify host-microbial interactions critical for human health.