Large-scale computational analyses of gut microbial CAZyme repertoires enabled by Cayman

Carbohydrate-active enzymes (CAZymes) are crucial for digesting glycans, but bioinformatics tools for CAZyme profiling and interpretation of substrate preferences in microbial community data are lacking. To address this, we developed a CAZyme profiler (Cayman) and a hierarchical substrate annotation scheme. Leveraging these, we genomically survey CAZymes in human gut microbes (n=107,683 genomes), which suggests novel mucin-foraging species. In a subsequent meta-analysis of CAZyme repertoires in Western versus non-Western gut metagenomes (n=4,281) we find that non-Western metagenomes are richer in fibre-degrading CAZymes despite lower overall CAZyme richness. We additionally pinpoint the taxonomic drivers underlying these CAZyme community shifts. A second meta-analysis comparing colorectal cancer patients (CRC) to controls (n=1,998) shows that CRC metagenomes are deprived of dietary fibre-targeting, but enriched in glycosaminoglycan-targeting CAZymes. A genomic analysis of co-localizing CAZyme domains predicts novel substrates for CRC-enriched CAZymes. Cayman is broadly applicable across microbial communities and freely available from https://github.com/zellerlab/cayman. ### Competing Interest Statement HT and ODB are employees of Societe des Produits Nestle, Switzerland, however Nestle was not involved in funding the study. HT and ODB contributed as experts on the topic.