<p>Carbohydrate-active enzymes (CAZymes) are crucial for digesting glycans, but tools for CAZyme profiling and interpretation of substrate preferences in microbiome data are lacking. Here we develop a CAZyme profiler called Cayman (Carbohydrate Active Enzymes Profiling of Metagenomes) and a hierarchical substrate annotation scheme for use with genomic or shotgun metagenomic datasets. Using these tools, we systematically surveyed CAZymes in human gut microorganisms (<i>n</i> = 107,683 genomes) and identified several putative mucin-foraging bacteria, including <i>Hungatella</i> and <i>Eisenbergiella</i> species, which were confirmed experimentally. We compared CAZymes in gut metagenomes (<i>n</i> = 3,960) from high-income settings versus low- and middle-income settings and found that low- and middle-income setting metagenomes are enriched in fibre-degrading CAZymes, while CAZyme richness is generally higher in high-income setting metagenomes. Additional analysis (<i>n</i> = 1,998) indicated that metagenomes of individuals with colorectal cancer are depleted in fibre-targeting and enriched in glycosaminoglycan-targeting CAZymes. Finally, we inferred CAZyme substrates from genomic co-localization of CAZyme domains. Cayman is broadly applicable and freely available from <a href="https://github.com/zellerlab/cayman">https://github.com/zellerlab/cayman</a>.</p>

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Cayman enables large-scale analysis of gut microbiome carbohydrate-active enzyme repertoires

  • Quinten R. Ducarmon,
  • Nicolai Karcher,
  • Samir Giri,
  • Hanne L. P. Tytgat,
  • Omar Delannoy-Bruno,
  • Selin Pekel,
  • Fabian Springer,
  • Patrick Wörz,
  • Christian Schudoma,
  • Athanasios Typas,
  • Georg Zeller

摘要

Carbohydrate-active enzymes (CAZymes) are crucial for digesting glycans, but tools for CAZyme profiling and interpretation of substrate preferences in microbiome data are lacking. Here we develop a CAZyme profiler called Cayman (Carbohydrate Active Enzymes Profiling of Metagenomes) and a hierarchical substrate annotation scheme for use with genomic or shotgun metagenomic datasets. Using these tools, we systematically surveyed CAZymes in human gut microorganisms (n = 107,683 genomes) and identified several putative mucin-foraging bacteria, including Hungatella and Eisenbergiella species, which were confirmed experimentally. We compared CAZymes in gut metagenomes (n = 3,960) from high-income settings versus low- and middle-income settings and found that low- and middle-income setting metagenomes are enriched in fibre-degrading CAZymes, while CAZyme richness is generally higher in high-income setting metagenomes. Additional analysis (n = 1,998) indicated that metagenomes of individuals with colorectal cancer are depleted in fibre-targeting and enriched in glycosaminoglycan-targeting CAZymes. Finally, we inferred CAZyme substrates from genomic co-localization of CAZyme domains. Cayman is broadly applicable and freely available from https://github.com/zellerlab/cayman.