Role of gut microbiota on regulation potential of Dendrobium officinale Kimura & Migo in metabolic syndrome: In-vitro fermentation screening and in-vivo verification in db/db mice

Dendrobium officinale Kimura & Migo (DEN) is a traditional medicine in China since Han dynasty. Decoction of its stem is often used in the treatment of Type-II diabetes (T2D), which is a typical metabolic disease accompanied with the impaired metabolic function of blood glucose and lipid. Our study aimed to investigate the role of gut microbiota in differentiating DEN from different sources and its related pathway in the alleviation of metabolic syndromes induced by T2D. The aqueous extracts of four commercially available Dendrobium (DEN-1∼4) were prepared and screened through an in-vitro fermentation system. Based on their alterations in monosaccharide composition and short chain fatty acids (SCFA) formation during fermentation with db/db faecal fluid, one DEN extract was selected for further in vivo verification. The selected Dendrobium (DEN-4) was orally administered to db/db mice for 16 days once daily at the dosage of 200 mg/kg followed by evaluating its effect on blood glucose level, liver function and intestinal microenvironment including alterations of intestinal integrity and gut microbiota composition. In addition, liver metabolomics analysis was employed to reveal the related metabolic pathways. Different extent of SCFA formation and utilization of monosaccharides were observed for the extracts of four DEN from different sources with a negative correlation between SCFA level and the ratio of Utilized glucose/Utilized mannose observed in the in-vitro fermentation system with db/db faecal fluid. DEN-4 with the highest SCFA formation during the in-vitro fermentation was selected and exhibited significantly hypoglycaemic effect in db/db mice with the alleviation of hepatic steatosis and impaired lipid homeostasis. Further mechanistic studies revealed that orally administered DEN-4 could improve the intestinal integrity of db/db mice via elevating their tight junction protein (ZO-1 and Occludin) expression in the colon and improve the diversity of gut microbiota with enhanced formation of SCFA. Moreover, metabolomics and KEGG pathway analysis of liver tissues suggested that the alleviated metabolic syndrome in db/db mice by DEN-4 might possibly be achieved through activation of PPAR pathway. Our current study not only revealed the potential of gut microbiota in differentiating DEN from different sources, but also demonstrated that DEN exhibited its beneficial effect on the T2D induced metabolic syndrome possibly through enhancement of intestinal integrity and activation of PPAR pathway via gut-liver axis in db/db mice.