AUTHOR=Cao Thao T. B. , Wu Kun-Chang , Hsu Jye-Lin , Chang Chih-Shiang , Chou Chiahung , Lin Chen-Yuan , Liao Yu-Min , Lin Pei-Chun , Yang Liang-Yo , Lin Hsiang-Wen 

TITLE=Effects of Non-insulin Anti-hyperglycemic Agents on Gut Microbiota: A Systematic Review on Human and Animal Studies

JOURNAL=Frontiers in Endocrinology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.573891

DOI=10.3389/fendo.2020.573891

ISSN=1664-2392

ABSTRACT=<p><bold>Background:</bold> As growing evidence links gut microbiota with the therapeutic efficacy and side effects of anti-hyperglycemic drugs, this article aims to provide a systematic review of the reciprocal interactions between anti-hyperglycemic drugs and gut microbiota taxa, which underlie the effect of the gut microbiome on diabetic control via bug-host interactions.</p><p><bold>Method:</bold> We followed the PRISMA requirements to perform a systematic review on human vs. animal gut microbiota data in PubMed, SCOPUS, and EMBASE databases, and used Cochrane, ROBIN-I, and SYRCLE tools to assess potential bias risks. The outcomes of assessment were trends on gut microbiota taxa, diversity, and associations with metabolic control (e.g., glucose, lipid) following anti-hyperglycemic treatment.</p><p><bold>Results:</bold> Of 2,804 citations, 64 studies (17/humans; 47/mice) were included. In human studies, seven were randomized trials using metformin or acarbose in obese, pre-diabetes, and type 2 diabetes (T2D) patients. Treatment of pre-diabetes and newly diagnosed T2D patients with metformin or acarbose was associated with decreases in genus of <italic>Bacteroides</italic>, accompanied by increases in both <italic>Bifidobacterium</italic> and <italic>Lactobacillus</italic>. Additionally, T2D patients receiving metformin showed increases in various taxa of the order <italic>Enterobacteriales</italic> and the species <italic>Akkermansia muciniphila</italic>. Of seven studies with significant differences in beta-diversity, the incremental specific taxa were associated with the improvement of glucose and lipid profiles. In mice, the effects of metformin on <italic>A. muciniphila</italic> were similar, but an inverse association with <italic>Bacteroides</italic> was reported. Animal studies on other anti-hyperglycemic drugs, however, showed substantial variations in results.</p><p><bold>Conclusions:</bold> The changes in specific taxa and β-diversity of gut microbiota were associated with metformin and acarbose in humans while pertinent information for other anti-hyperglycemic drugs could only be obtained in rodent studies. Further human studies on anti-hyperglycemic drugs other than metformin and acarbose are needed to explore gut microbiota's role in their therapeutic efficacies and side effects.</p>