Effects of Acarbose on the Gut Microbiota of Prediabetic Patients: A Randomized, Double-blind, Controlled Crossover Trial

INTRODUCTION The α-glucosidase inhibitor acarbose is an efficacious medicine for the treatment and prevention of type 2 diabetes mellitus (T2DM). However, the response of gut microbiota to acarbose is important, as the microbiota may have a critical role in the development of metabolic diseases, and acarbose is metabolized exclusively within the gastrointestinal tract. We explored the changes in the proportion and diversity of gut microbiota before and after treatment with acarbose in patients with prediabetes. METHODS We designed a randomized, double-blind, controlled crossover trial in which 52 Chinese patients with prediabetes by an oral glucose tolerance test (OGTT) with a BMI of 18-35 kg/m2 were randomly allocated to treatment with acarbose or placebo. Gut microbiota characterizations were determined with 16S rDNA-based high-throughput sequencing. RESULTS Of the 52 participants who entered the study, 40 (76.9%) completed the protocol. On the basis of the operational taxonomic unit (OTU) profiles, a total of 107 OTUs were significantly altered after acarbose treatment, with 76 (71%) assigned to the order of Clostridiales. Ruminococcaceae (15 OTUs) and Lachnospiraceae (22 OTUs) decreased in response to acarbose, and 48 OTUs increased by 12.8-fold, including Lactobacillaceae (8 of 9 belonging to Lactobacillus), Ruminococcaceae (6 of 11 belonging to Faecalibacterium), and Veillonellaceae (8 of 15 belonging to Dialister). At genera level, five flourished after treatment with acarbose, including Lactobacillus and Dialister, while Butyricicoccus, Phascolarctobacterium, and Ruminococcus were inhibited. CONCLUSION This study suggests that the benefits of acarbose for T2DM may correlate with the selective modulation of the gut microbiota. TRIAL REGISTRATION Chinese Clinical Trial Register number, ChiCTR-TTRCC-13004112.