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

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 fromhttps://github.com/zellerlab/cayman.

Unraveling interindividual differences and functional consequences of gut microbial metabolism of immunosuppressants

“… (A) Schematic of the assay. (B) Principal Coordinates Analysis (PCoA) comparing the composition of 38 human-derived gut microbial communities, cultivated under anaerobic conditions for 8 hours before sequencing, to 3189 reference human gut microbial metagenomes from 10 datasets in industrialized countries (corresponding to the Westernized control samples used in ( 30 ), Table S2). Circles and triangles denote the tested communities, color-coded by population source (see inset).…”

“…Preprocessed reads were then mapped to the human gut specific Global Microbial Gene Catalogue (GMGC) ( 29 ) using BWA-MEM (0.7.17) with default parameters. Here, a reduced GMGC catalog excluding very rare genes was used (described in ( 30 )). Alignments were filtered to >45bp alignment length and >97% sequence identity and profiled with gffquant version v2.9.1 (https://github.com/cschu/gff_quantifier).…”

Long-term fasting remodels gut microbial metabolism and host metabolism

“…In order to obtain information on the taxonomic origin of CAZymes, we first annotated high-quality genomes from Almeida et al 24 , which amounted to a total of 101,229 metagenome-assembled genomes (MAGs) and 6,456 isolate genomes, as previously described 13 . We then calculated mean CAZyme family copy numbers and prevalences per species on all genomes belonging to the respective species.…”

“…Raw reads were cleaned as described previously 13 . Taxonomic profiling was performed using mOTUs (v3.1) with default parameters on these quality-filtered reads; species abundance profiles referred to in the following were technically mOTU abundances and species names are followed by mOTUs identifiers in brackets.…”

“…Gut microbial modules (GMM) were inferred based on KOs and the R package omixerRpm v_0.3.3 using default parameters 14 . Profiling of carbohydrate-active enzymes was done using Cayman (v0.9.6) 13 .…”