Regulating the gut microbiota and SCFAs in the faeces of T2DM rats should be one of antidiabetic mechanisms of mogrosides in the fruits of Siraitia grosvenorii

The Siraitia grosvenorii fruits extract (SG, in which mogrosides are the main components), considered as a non-nutritional sweetener, has an antidiabetic effect. Our previous studies have confirmed that an extract of mogrosides being rich in triterpene glycosides with 1–3 glucosyl residues, designated as low-polar S. grosvenorii glycosides (L-SGgly), had a significant antidiabetic effect. However, whether the mechanism through impacting on gut microbiota to exert the antidiabetic effect of mogrosides remains unclear. To explore the potential mechanism of mogrosides (SG and L-SGgly) on gut microbiota and faecal metabolites in the treatment of diabetes. In this study, the effects of SG and L-SGgly on gut microbiota and faecal endogenous metabolites were explored by sequencing the 16S rRNA V3–V4 region of gut microbiota, and detecting with gas chromatography-mass spectrometry (GC-MS) and liquid chromatography quadrupole time-of-flight MS (LC-Q-TOF/MS), respectively. In particular, correlation analyses revealed how these influences affect the anti-hyperglycaemic effect, to give the underlying antidiabetic mechanisms of the mogrosides in S. grosvenorii fruits. After a 14-day treatment with SG and L-SGgly for type 2 diabetes mellitus (T2DM) rats induced by a high-fat diet (HFD) and streptozotocin (STZ), the disordered gut microbiota in the faeces of T2DM rats were recovered. At the same time, the short-chain fatty acids (SCFAs) concentration significantly increased and the deoxycholic acid and 1β-hydroxycholic acid content decreased in the faeces of T2DM rats. Moreover, correlation analyses provided the evidences that gut microbiota and its metabolites could be the target for exerting the anti-hyperglycaemic effects of SG and L-SGgly. Especially, Elusimicrobium, Lachnospiraceae_UCG-004, acetate, butyrate, and 1β-hydroxycholic acid would be the potential dominant bacteria and biomarkers for SG and L-SGgly in reducing the blood glucose and insulin resistance of T2DM rats. It is the first time that a mechanism of targeting on gut microbiota for the antidiabetic effect of mogrosides in S. grosvenorii fruits has been proposed.