Abstract
Type 1 diabetes (T1D) is a serious health problem that needs to be addressed worldwide. Astragalus polysaccharides (APS), the main chemical components of Astragali Radix, have anti-diabetic activity. As most plant polysaccharides are difficult to digest and absorb, we hypothesised that APS exert hypoglycaemic effects through the gut. This study intends to investigate the modulation of T1D associated with gut microbiota by neutral fraction of Astragalus polysaccharides (APS-1). T1D mice were induced with streptozotocin and then treated with APS-1 for 8 weeks. Fasting blood glucose levels were decreased and the insulin levels were increased in T1D mice. The results demonstrated that APS-1 improved gut barrier function by regulating ZO-1, Occludin and Claudin-1 expression, and reconstructed gut microbiota by increasing the relative abundance of Muribaculum, Lactobacillus and Faecalibaculum. In addition, APS-1 significantly increased the levels of acetic acid, propionic acid, butyric acid and inhibited the expression of pro-inflammatory factors IL-6 and TNF-α in T1D mice. Further exploration revealed that APS-1 alleviation of T1D may be associated with short-chain fatty acids (SCFAs)-producing bacteria, and that SCFAs binds to GPRs and HDACs proteins and modulate the inflammatory responses. In conclusion, the study supports the potential of APS-1 as a therapeutic agent for T1D.