Discovering microbiota functions via chemical probe incorporation for targeted sequencing

Our microbiota plays crucial roles in immune development and homeostasis and has been implicated in virtually all major diseases of the 21st century. Nevertheless, our understanding of the exact microbial functions that underlie these correlations remains extremely limited, due in large part to the difficulty of profiling cellular activities within non-model organisms and complex communities. Over the past decade, new flow cytometric approaches have been developed to distinguish specific microbial populations based on their interactions with metabolite analogs, modified biomolecules, and reactive compounds. By selecting and separating active microbes via fluorescence-activated cell sorting, PRobe INcorporation for Targeted sequencing (PRINT-seq) has inspired innovative approaches to identify and characterize functional members of our microbiota. Here, we provide a broad overview of this evolving technology and summarize how this method has been recently employed as a diagnostic fingerprint for diverse microbial activities.