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Type 2 diabetes is a leading cause of morbidity and a common risk of several disorders. Identifying the microbial ecology changes is essential for disease prediction, therapy, and prevention. Thus, our study is aimed at investigating the intestinal microbiota among healthy and type 2 diabetes individuals and exploring the effect of antidiabetic agents on gut bacterial flora. 24 type 2 diabetes (metformin, glimepiride, and nontherapeutic subgroups; N = 8) and 24 healthy control subjects were enrolled in this study, and intestinal bacterial microbiota was investigated by analyzing V3-V4 regions of 16S rRNA gene sequence. Numerous alterations were observed in the gut microbial community of diabetic individuals. These changes were characterized by a significant lowered abundance of Faecalibacterium , Fusobacterium , Dialister , and Elusimicrobium in the nontherapeutic subgroup compared to the healthy control group. Likewise, correlation analysis showed a substantial decline in gut microbiota richness and diversity with the duration of illness. Furthermore, antidiabetic agents restored to some extent the richness and diversity of gut microbiota and improved the abundance of many beneficial bacteria with a significant increase of Methanobrevibacter in the metformin subcategory compared to the nontherapeutic subgroup. In return, they decreased the abundance of some opportunistic pathogens. The findings of this study have added a novel understanding about the pathogenesis of the disease and the mechanisms underlying antidiabetic therapy, which are of potential interest for therapeutic lines and further studies., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Babiker Saad Almugadam et al.)