Synergistic antihyperglycemic effects of wheat bran insoluble dietary fiber–inulin complex via gut microbiota mediated short-chain fatty acid production

The synergistic antihyperglycemic effects of wheat bran insoluble dietary fiber (WBIDF) complexed with inulin (IN) were investigated in this study. In vitro fecal fermentation demonstrated that WBIDF-IN significantly increased the production of short-chain fatty acids (SCFAs), particularly acetic and butyric acids, outperforming WBIDF and other WBIDF-soluble dietary fiber (SDF) complexes (including WBIDF-stachyose, WBIDF-fructo-oligosaccharides, and WBIDF-resistant dextrin). Subsequently, db/db mice received the optimized complex for 12 weeks. Compared with WBIDF or IN alone, WBIDF-IN supplementation significantly lowered fasting blood glucose, improved glucose tolerance, enhanced insulin sensitivity by reducing fasting insulin and HOMA-IR, and promoted GLP-1 secretion. HE staining revealed that WBIDF-IN markedly preserved islet morphology and cellular integrity, while immunofluorescence analysis confirmed the restoration of insulin expression to near-normal levels. 16S rRNA sequencing revealed that WBIDF-IN improved gut microbial diversity and shifted the microbial composition by enriching SCFAs-producing genera such as Muribaculaceae, Ruminococcaceae, and Alloprevotella, while reducing harmful taxa like Romboutsia and Enterococcus. Correlation analysis further revealed that the relative abundance of Alloprevotella was positively associated with colonic SCFAs and GLP-1 levels, but negatively correlated with fasting blood glucose. Collectively, these findings demonstrated that WBIDF-IN complexation exerts enhanced antihyperglycemic effects primarily through microbiota-mediated SCFAs production, which promoted GLP-1 secretion and pancreatic islet protection, providing a promising dietary strategy for type 2 diabetes management.