Gut microbiota and intestinal FXR siganlling involved in the alleviation of mulberry (Morus alba L.) leaf ethanol extract on type 2 diabetes mellitus in db/db mice

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The potential mechanism of mulberry leaf against type 2 diabetes mellitus (T2DM) is not fully elucidated. Here, we hypothesized that the anti-T2DM of mulberry leaf ethanol extract (MLEE) is related to improvement of gut microbiota and bile acids (BAs) metabolism. Our results showed that MLEE alone can ameliorate glycolipid metabolism disorder, insulin resistance, and inflammation in db/db mice, and presents synergistic effects with metformin (MET). Furthermore, we found that MLEE altered the abundances of gut microbiota related to BAs metabolism such as Colidextribacter, Muribaculum, Muribaculaceae, and Eubacterium_siraeum_group, promoted fecal ωMCA level and thus inhibited intestinal farnesoid X receptor (FXR) gene expression, and then increased plasma glucagon-like peptide-1 (GLP-1) level. Furthermore, intestinal FXR inhibition and plasma GLP-1 level enhancing of MLEE could also be observed in antibiotic-intervened db/db mice. These results indicated that MLEE could alleviate T2DM via gut microbiota-BAs-intestinal FXR pathway mediated by gut microbiota and host.