Jiang Tang San Hao Formula exerts its anti-diabetic effect by affecting the gut-microbiota-brain axis

Type 2 diabetes is a complex metabolic disorder characterized by insulin resistance and impaired insulin secretion, with growing evidence highlighting the critical role of the gut-microbiota-brain axis in modulating glucose and lipid metabolism.

To evaluate the effects of Jiang Tang San Hao Formula (JTSHF) on blood glucose control in type 2 diabetic mouse model and to explore its mechanism through the gut- microbiota-brain axis.

A type 2 diabetes model was established using six-week-old male C57BL6/J mice, induced by a high-fat diet combined with streptozotocin injection. The diabetic mice then randomly assigned to the model group, metformin (Glucophage) group and JTSHF group, receiving 11 weeks of treatment by gavage. Body weight and fasting blood glucose were monitored biweekly. The oral glucose tolerance test was performed during the fifth and 10th weeks of the intervention. The measurements of body composition were conducted pre- and post-treatment. After the intervention, serum insulin, lipid levels, glucagon like peptide-1 (GLP-1), peptide YY, ghrelin, and leptin were detected. The fresh feces of mice were collected before sacrifice for gut microbiota analysis and short chain fatty acids quantification. The colon tissues of mice in each group were collected to observe the morphological structure and to measure the expression levels of GPR41 and GPR43. The hypothalamus was collected to assess the expression of POMC, AgRP and NPY.

JTSHF significantly boosted sugar and lipid metabolism and contributed to weight reduction in diabetic mice (p < 0.05). At the genus level, JTSHF increased the relative abundance of Bacteroides, Prevotella, and Parabacteroides, and decreased Clostridium, Lactobacillus, and Oscillibacter in the gut microbiota. JTSHF enhanced the content of short chain fatty acids, improved the expression level of GPR43/41 in colonic tissue (p < 0.05), and increased POMC expression while decreasing AgRP and NPY expression in the hypothalamus (p < 0.05). Serum GLP-1 was increased, and ghrelin was decreased significantly after JTSHF intervention (p < 0.05).

By affecting the composition, relative abundance, and metabolites of gut microbiota, JTSHF regulates various gut brain peptides, affects the hypothalamic feeding center, improves glucose and lipid metabolism, and thus plays the anti-diabetic role. The study provides novel insights into how traditional Chinese medicine modulates the gut-brain connection to exert anti-diabetic effects, highlighting the innovative potential of JTSHF in metabolic disease management.