Gut microbiota carbohydrate transporters and glycosidases

Gut microbiota carbohydrate transporters and glycosidases are a vast array of bacterial proteins essential for the degradation and internalization of complex carbohydrates that escape human digestion. These proteins, including Glycoside Hydrolases (GHs) and components of Polysaccharide Utilization Loci (PULs), enable the production of short-chain fatty acids (SCFAs) like butyrate and acetate, which regulate host immunity and energy balance (Lombard et al., 2014; Martens et al., 2009). In clinical contexts, these enzymes are significant because they can reactivate glucuronidated drug metabolites in the intestinal lumen, causing site-specific toxicity; a prime example is the reactivation of the SN-38 metabolite of irinotecan by bacterial beta-glucuronidases, leading to severe intestinal damage (Wallace et al., 2010). Pharmacological targeting of these systems involves using small-molecule inhibitors to mitigate drug side effects or using prebiotics to shift the microbial population toward a healthier metabolic profile. Consequently, these transporters and enzymes are pivotal targets for treating metabolic syndrome, inflammatory bowel diseases, and improving the therapeutic index of various medications.

Other names

Carbohydrate-active enzymesCAZymesGlycoside hydrolasesPolysaccharide utilization lociMicrobial sugar transportersBacterial beta-glucuronidases

Inhibition of glycoside hydrolase activity to delay carbohydrate absorption; competitive inhibition of bacterial beta-glucuronidases to prevent drug reactivation; prebiotic-mediated modulation of microbial fermentation pathways.