Hypoglycemic effects of different molecular weight konjac glucomannans via intestinal microbiota and SCFAs mediated mechanism

The hypoglycemic effects of konjac glucomannans (KGMs) are well recognized, and our previous study showed KGMs with different molecular weight have different hypoglycemic effects on diabetes rats, but the detailed mechanisms still remain unclear. In this study, KGMs with medium molecular weight (KGM-M, 757.1 kDa) and low molecular weight (KGM-L, 87.3 kDa) were utilized to investigate the possible mechanism on hypoglycemic effects of type 2 diabetic (T2DM) rats. The results revealed that KGM-M had better effects than KGM-L on decreasing fasting blood glucose, mitigating insulin resistance and improving inflammation. Further mechanism analysis showed that KGM-M better enriched gut flora diversity and the abundance of Ruminococcus and Lachnoclostridium, which was accompanied by increased short chain fatty acids (SCFAs) production and expression of G protein-coupled receptors (GPCRs), and improved regulation on bile acid synthesis. Antibiotics treatment eliminated the beneficial effects of KGMs on gut flora, SCFAs, GPCRs and bile acid synthesis. By contrast, fecal microbiota transplantation (FMT) treatment restored the structure of intestinal microbiota. And after FMT treatment, KGM-M displayed higher hypoglycemic activity than KGM-L, probably due to the better effects on intestinal microbiota, SCFAs production, GPCRs expression and bile acid synthesis inhibition.