Intestinal Microbiota Composition in Patients with Type 2 Diabetes and Effects of Oral Antidiabetics

Introduction: The cause-effect relationships between microbiota composition changes and type 2 diabetes (T2D) are complex, likely involving two-way interactions, and require further elucidation. Few studies have examined the interactions of antidiabetic drugs with the gut microbiota. This study's goal was to evaluate the gut microbiota of patients with type 2 diabetes at first diagnosis and again after 12 weeks of taking oral antidiabetic drugs. Methods: We performed a fecal microbiota analysis of adult patients who recently received a T2D diagnosis and healthy adults. We compared the microbiota compositions between the T2D patients and healthy controls; we also evaluated changes from baseline to 12 weeks of treatment in the total group receiving oral antidiabetics, as well as in the subgroups receiving metformin and linagliptin. Results: The alpha diversity and beta diversity indices were different at baseline between patients with type 2 diabetes and healthy controls. The LEfSe analysis showed that, at the genus level, the Lactobacillus, Rothia, Collinsella, and Eubacterium genera increased in relative abundance in the T2D group while, at the species level, the Rothia mucilaginosa, Collinsella aerofaciens, and Eubacterium bioforme strains were found to be dominant in the T2D group. Faecalibacterium at the genus level and Faecalibacterium prausnitzii at the strain level increased in relative abundance in the T2D group after 12 weeks. After 12 weeks of intervention, the alpha diversity indices were significantly lower in the T2D group compared to the control group. At the end of the 12th week, the Gemmiger and Collinsella genera were dominant in the T2D group, with Gemmiger formicilis and Collinsella aerofaciens being dominant at the species level; in the control group, Bacteroides and Alistipes were dominant at the genus level, and Prevotella stercorea and Alistipes finegoldii were dominant. There was no difference in the LEfSe analysis results between baseline and 12 weeks of linagliptin treatment. At the strain level, Gemmiger formicilis, Ruminococcus bromii, Rothia mucilaginosa, and Lactobacillus ruminis were predominant at the start of metformin treatment; however, after 12 weeks, Collinsella aerofaciens became predominant. Conclusions: We report that there is a substantial change in the composition of the gut microbiota in patients with T2D. Oral antidiabetic treatments, especially metformin, have some beneficial effects on microbiota composition. Few studies have explored the interaction of antidiabetic drugs with the gut microbiota; further research will elucidate the clinical impact of these changes in gut microbiota composition in diabetes.