16S rRNA Sequencing and Metagenomics Study of Gut Microbiota: Implications of BDB on Type 2 Diabetes Mellitus.

Gut microbiota has a critical role in metabolic diseases, including type 2 diabetes mellitus (T2DM). 3-bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (BDB) is a natural bromophenol isolated from marine red alga Rhodomela confervoides. Our latest research showed that BDB could alleviate T2DM in diabetic BKS db mice. To find out whether BDB modulates the composition of the gut microbiota during T2DM treatment, 24 BKS db diabetic mice were randomly grouped to receive BDB (n = 6), metformin (n = 6), or the vehicle (n = 6) for 7 weeks in a blinded manner. Non-diabetic BKS mice (n = 6) were used as normal control. Diabetic mice treated with BDB or metformin demonstrated significant reductions in fasting blood glucose (FBG) levels compared with the vehicle-treated mice in the 7th week. Pyrosequencing of the V3–V4 regions of the 16S rRNA gene revealed the changes of gut microbiota in response to BDB treatment. The result demonstrated short-chain acid (SCFA) producing bacteria Lachnospiraceae and Bacteroides were found to be significantly more abundant in the BDB and metformin treated group than the vehicle-treatment diabetic group. Remarkably, at the genus levels, Akkermansia elevated significantly in the BDB-treatment group. Metagenomic results indicated that BDB may alleviate the metabolic disorder of diabetic mice by promoting propanoate metabolism and inhibiting starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism. In conclusion, our study suggests that the anti-diabetic effect of BDB is closely related to the modulating structure of gut microbiota and the improvement of functional metabolism genes of intestinal microorganisms.