Acarbose differentially affects gut microbial metabolism of maltose and sucrose, distinctly modulating host metabolism.

Gut microbiota act as beneficial symbionts of the hosts. Administration of α-glucosidase inhibitors (α-GIs) is considered to promote the microbiota's carbohydrate availability, modulating short-chain fatty acid (SCFA) production. However, it remains unclear whether host-microbiota interaction differs depending on α-GI types (e.g., acarbose versus miglitol) and carbohydrate types co-administered. In this study, we demonstrate that acarbose is transported through bacterial outer membrane porins, LamB and ScrY, and inhibits maltose metabolism in Escherichia coli. Furthermore, studies using Klebsiella pneumoniae reveal that acarbose suppresses utilization of maltose, but not that of sucrose. When co-administered with acarbose in mice, sucrose, relative to maltose, enhances SCFA production, suppresses glucose-dependent insulinotropic polypeptide (GIP) secretion, and protects against high-fat diet-induced obesity, underscoring the importance of sucrose as a microbiota-dependent beneficial factor, but not a culprit in host metabolism. In conclusion, acarbose regulates host metabolic processes partly by modulating gut microbial metabolism in a carbohydrate-type-dependent manner.