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bioRxiv · 10.1101/2024.01.08.574624

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

Ducarmon, Q. R.·Karcher, N.·Tytgat, H. L. P.·Delannoy-Bruno, O.·Pekel, S.·Springer, F.·Schudoma, C.·Zeller, G.
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Abstract

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.

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Ducarmon, Q. R., Karcher, N., Tytgat, H. L. P., Delannoy-Bruno, O., Pekel, S., Springer, F., Schudoma, C., Zeller, G.. 2024-01-08. Large-scale computational analyses of gut microbial CAZyme repertoires enabled by Cayman. https://doi.org/10.1101/2024.01.08.574624

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