Neohesperidin dihydrochalcone can improve intestinal structure and microflora composition of diabetic zebrafish

This study focused on Neohesperidin dihydrochalcone (NHDC) and explored its effects on the intestinal tissue structure, short-chain fatty acid production, gut microbiota, and intestinal tissue oxidative stress in a diabetic zebrafish model with insulin resistance. By analyzing the relationship between gut microbiota changes and glucose metabolism, it revealed the mechanism through which NHDC improves insulin resistance by modulating the gut microbiota. The results indicate that NHDC intervention has a protective effect on the intestinal barrier in diabetic zebrafish, improving lipid metabolism disturbances, and enhancing intestinal antioxidant capacity. Regarding community diversity, NHDC treatment increased the diversity and richness of the gut microbiota in diabetic zebrafish. In terms of gut microbiota composition, NHDC treatment reduced the abundance of the inflammation-associated Proteobacteria while increasing the relative abundance of the Fusobacteria, thereby maintaining the stability of the zebrafish gut microbiota. Furthermore, NHDC treatment also increased the abundance of the Prevotella, which is beneficial for increasing glycogen storage and inhibiting liver gluconeogenesis. Therefore, we speculate that NHDC may regulate the production of SCFAs and reduce the expression levels of pro-inflammatory cytokines by reducing the abundance of harmful bacteria such as Proteobacteria, Plesiomonas, and Aeromonas, while increasing the abundance of Faecalibacterium and Fusobacteria. The changes in the abundance of these microbiota members are involved in processes such as inflammation stress, glycogen storage, and gluconeogenesis, collectively promoting the improvement of insulin resistance in diabetic zebrafish by NHDC.