Gut microbiota profiling revealed the regulating effects of salidroside on iron metabolism in diabetic mice

BACKGROUND: Diabetes is a common metabolic disease that is associated with gut microbiota dysbiosis and iron metabolism. Salidroside (SAL) is the main ingredient of the traditional Chinese herb Rhodiola, previous studies have shown that SAL could reshape the gut microbiota and limit iron accumulation. Therefore, it is possible that SAL can act as an alternative therapy for diabetes, and its underlying mechanism is worth exploring. METHODS: SAL was used to treat diabetic db/db mice. Serum glucose and iron levels and the histopathology of myocardial fibres were evaluated. The gut microbiota composition was determined by 16S rRNA Illumina sequencing technology. RESULTS: Treatment with SAL significantly reduced blood glucose and ameliorated diabetic cardiomyopathy in diabetic db/db mice, which was accompanied by inhibited ferroptosis and iron accumulation. Furthermore, the 16S rRNA sequencing results showed that SAL induced a change in the gut microbiota composition. Overall, SAL could increase the proportion of probiotic bacteria and decrease Lactobacillus to improve gut microbiota. Specifically, SAL increased the ratio of Bacteroidetes to Firmicutes in diabetic mice. The most significant biomarker was the genus Lactobacillus between the MD group and the SAL group. In addition, COG and KEGG analyses suggested that SAL mainly participated in nutrient metabolism, among them iron metabolism was associated with the abundance of Lactobacillus. CONCLUSIONS: SAL could reduce the glucose level and protect against diabetic cardiomyopathy in diabetic mice, which might be mediated by the change in the gut microbiota and the regulation of iron metabolism. The findings suggested that SAL was a promising complementary option for diabetes therapy.