Daidzein improved glucose homeostasis via PI3K/AKT and modulated the communities of gut microbiota in turbot (Scophthalmus maximus L.)

The glucose intolerance of fish limits its carbohydrate utilization. It is of practical significance to improve the glucose tolerance of fish, especially carnivorous fish in aquaculture. Daidzein, one of the most abundant soy isoflavones in legumes, has been proved to have positive effects on glucose homeostasis. In present study, the effects of daidzein on glucose tolerance and hepatic glucose metabolism were investigated in marine carnivorous fish turbot (Scophthalmus maximus L.). The results of oral glucose tolerance test found that oral administration of daidzein improved the glucose tolerance of turbot and promoted the insulin secretion in the serum of turbot. In vitro, daidzein promoted glucose consumption, suppressed hepatic glucose production and improved insulin sensitivity in primary hepatocytes. Then, both in vivo and in vitro studies found that daidzein activated phos-phoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. While blocking PI3K/AKT signaling pathway with PI3K inhibitor, the beneficial effects of daidzein on hepatic glucose metabolism in primary he-patocytes were abolished. Besides, oral administration of daidzein significantly altered the microbiota profiles, which increased the abundance of Bacteroidota, decreased the ratio of Firmicutes/Bacteroidota and the abun-dance of potential pathogen such as Ralstonia and Pseudomonas. In conclusion, daidzein improved glucose ho-meostasis via PI3K/AKT signaling pathway, and the intestinal microbiota might also be involved in this process.