Curative effects of dietary secoisolariciresinol diglucoside on type 2 diabetes: action and mechanism

The prevalence of Type 2 Diabetes Mellitus (T2DM) is on the rise annually and few therapeutic options are truly curative. Previous studies have shown circumstantial evidence on the effects of lignans to alleviate T2DM. In this study, we established a diabetic mouse model to validate the effects and elucidate the therapeutic mechanisms of the lignans on diabetes. We used two forms of plant lignans, defatted flaxseed meal (DFM) and secoisolariciresinol (SECO). We treated the mice by oral administration of the lignans, which can be converted to enterolactone (ENL) by gut bacteria to exert physiological or medical actions. After 8 weeks of oral administration, the lignans significantly alleviated diabetic conditions in the mice, recovering body weight and reducing the levels of blood glucose, blood lipids, and inflammatory factors. The lignans significantly ameliorated the disordered gut microbiome and increased the abundance of bacterial taxa beneficial for alleviating diabetes, such as Bifidobacterium animalis and Bifidobacterium pseudolongum . Metabolomics analysis revealed significant changes in intestinal metabolites such as ENL, which was low in the fecal metabolome of diabetic mice but significantly increased after oral administration of DFM or SECO. Spearman correlation analysis showed a significant negative correlation between ENL levels and diabetes. Proteomic results from mouse liver tissue showed that DFM and SECO could upregulate the expression of proteins that are involved in the regulation of blood glucose, such as Gck and Pklr. We conclude that lignans can effectively alleviate diabetes by ameliorating gut microbiome and upregulating proteins that modulate glucose metabolism.