PURPOSE

This study aims to assess the therapeutic potential of combining Shen-Ling-Bai-Zhu-San (SLBZS) or prebiotics with intermittent fasting (IF) in type 2 diabetes mellitus (T2DM) mice and to investigate the synergistic effects and underlying mechanisms.

METHODS

Type 2 diabetic mouse models were induced using high-fat diet (HFD) and streptozotocin (STZ), followed by IF treatment. Mice were then grouped for combined therapy with different doses of SLBZS and prebiotics. Fasting blood glucose (FBG) levels, body weight variations, and oral glucose tolerance tests were assessed to elucidate metabolic alterations. The hepatic and renal parameters were evaluated to determine systemic changes in T2DM mice, while the insulin levels were quantified by ELISA to assess glucose homeostasis. Gut microbiota alterations were examined via 16S rRNA sequencing. Alterations of the genes in relevant signaling pathways were analyzed using RT-qPCR.

RESULTS

IF improved FBG, body weight, insulin levels, and other diabetes indicators. Combined IF with SLBZS or prebiotics yielded similar effects. Furthermore, it ameliorated dyslipidemia and mitigated hepatic and renal parameters in T2DM mice. Pancreatic tissue histopathology showed islet cell restoration post-intervention. IF therapy reduced the abnormally elevated gene expression and increased the abnormally reduced genes. Further analysis indicated that the combination of IF with prebiotics and high doses of SLBZS upregulated the expression of the and genes. Gut microbiota analysis revealed restored diversity and structure, with notable changes in specific bacterial families. At the family level, the contents of and were restored. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) analysis suggested metabolic pathway alterations.

CONCLUSION

IF improved type 2 diabetic symptoms, with combined SLBZS and prebiotics showing similar effects. IF with high concentration of SLBZS and prebiotics doses upregulated the and genes and had superior effects on gut microbiota compared to IF alone.