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.