Structural characteristics of a polysaccharide isolated from Lactaruis volemus Fr. and its anti-diabetic effects regulated by the modulation of gut microbiota and metabolites.

As natural bioactive compounds, polysaccharides have promising effects in the treatment of type 2 diabetes mellitus (T2DM) owing to their changes to the intestinal microenvironment; however, the mechanisms underlying their effects have not been elucidated. In the present study, a polysaccharide LV-P4-1 isolated from Lactaruis volemus Fr was purified and characterized. The hyperglycemic function and the regulatory effect of LV-P4-1 on the gut microbiota and its metabolites were investigated in a T2DM mouse model. LV-P4-1 was mainly consisted of Fuc, Gal, Glc, Man, and GlcA, with a molecular weight of 5.89 kDa. The functional groups and glycosyl linkage types of LV-P4-1 were investigated using Fourier transform infrared spectroscopy, methylation and nuclear magnetic resonance analyses. Oral administration of 400 mg/kg LV-P4-1 increased glucose metabolism and alleviated tissue damage in mice with T2DM. Moreover, LV-P4-1 significantly regulated the abundances of gut microbiota, changed metabolite levels, and altered some metabolic pathways involved in T2DM development. Spearman analysis showed that the alterations in the gut microbiota were closely related to the differential metabolites. These results suggest that LV-P4-1 may alleviate hyperglycemia by influencing the structure of the intestinal microbiota and regulating the metabolic profile by altering the activity of certain metabolic pathways.