Colonic microbiota carbohydrate-active enzymes (CAZymes)

Colonic microbiota carbohydrate-active enzymes (CAZymes) are a vast repertoire of enzymes encoded by the gut microbiome that are responsible for the breakdown, modification, and biosynthesis of complex carbohydrates (Kaoutari et al., 2013, Nature Reviews Microbiology). While the human genome encodes fewer than 100 enzymes for carbohydrate digestion, the gut microbiota provides thousands of CAZymes, including glycoside hydrolases, polysaccharide lyases, and carbohydrate esterases, enabling the fermentation of otherwise indigestible dietary fibers (Drula et al., 2022, Nucleic Acids Research). This fermentation process produces short-chain fatty acids (SCFAs) such as butyrate, propionate, and acetate, which serve as vital energy sources for colonocytes and act as signaling molecules in systemic metabolism and immune regulation (Koh et al., 2016, Cell). Alterations in the CAZyme landscape are associated with various pathologies, including obesity, type 2 diabetes, and inflammatory bowel disease (IBD), where specific enzymatic activities may contribute to excessive energy harvest or the degradation of the protective intestinal mucus layer (Desai et al., 2016, Cell). Therapeutic targeting of CAZymes involves the use of prebiotics to selectively enrich beneficial enzymatic functions or small-molecule inhibitors like acarbose to modulate glucose release and absorption (Zhang et al., 2017, Nature Communications). Consequently, CAZymes are pivotal targets for nutritional and pharmacological interventions aimed at restoring metabolic health and intestinal homeostasis.

Other names

Gut microbial CAZymesCarbohydrate-active enzymesMicrobial glycoside hydrolasesGlycan-degrading enzymesMicrobiome CAZymes

CAZymes are targeted through competitive inhibition of specific glycoside hydrolases to slow carbohydrate breakdown and glucose absorption, or through the provision of prebiotic substrates that act as selective fermentable sources to shift the microbial enzymatic landscape and increase short-chain fatty acid production (Zhang et al., 2017, Nature Communications; Gibson et al., 2017, Nature Reviews Gastroenterology & Hepatology).