Simiao Wan modulates the gut microbiota and bile acid metabolism during improving type 2 diabetes mellitus in mice

Gut microbiota coupled with their metabolites (bile acids, BAs) get involved in diabetic pathogenesis. Simiao Wan is a famous traditional Chinese formula consisting on Phellodendron chinense C.K.Schneid. (Rutaceae), Atractylodes lancea (Thunb.) DC. (Asteraceae), Achyranthes bidentata Blume (Amaranthaceae) and Coix lacryma-jobi var. ma-yuen (Rom.Caill.) Stapf (Poaceae), and used to treat gouty arthritis and hyperuricemia for thousands of years. However, the mechanisms underlying its beneficial efficacy on diabetes still needs to be explored. Our study was performed to reveal the effects of the 75% ethanol extraction of Simiao Wan (SMW) on diabetes, gut microbiota and bile acids (BAs) in diabetic mice. The effects of SMW on diabetes were evaluated in mice treated by high-fat diet (HFD)/streptozotocin (STZ). The 16S rDNA sequencing and BAs metabolomics were performed to assess the changes of BAs profiles and gut microbiota induced by SMW. Western blot and real-time quantitative PCR were conducted to evaluate the possible mechanism of SMW. SMW significantly improved insulin resistance and hepatic lipid accumulation in HFD/STZ mice. It remarkably enriched in the bacteria Allobaculum, Clostridium, Akkermansia, Lactobacilus and Bilophila whereas decreased Coprococcus and Halomonas in diabetic mice. Furthermore, the profiles of BAs were also modulated by SMW, indicated by the reduction of conjugated BAs and 12α-OH/non-12α-OH BAs ratio in liver as well as the increase of primary BAs in feces. SMW also activated farnesoid X receptor and inhibited sterol regulatory element-binding protein-1 expression, contributing to its beneficial actions on lipid accumulation in liver. Our results showed that SMW exerted its beneficial effects on insulin resistance and hepatic lipid accumulation indirectly through regulating profiles of gut microbe and BAs.