Bovine lactopontin promotes bone development in growing rats by altering the composition of intestinal flora and bile acid metabolism

Lactopontin (LPN) is an important milk protein with the potential to improve bone health; however, its specific effects have not been determined. This study aims to investigate the effects of LPN on early bone growth and development. 3 week-old SD rats (<i>n</i> = 32) were assigned to the control group, whey protein concentration (WPC) group, LPN-L (low-dose LPN) group, and LPN-H (high-dose LPN) group, with intragastric administration of deionized water, 65.8 mg kg^-1 WPC, and 5 and 45 mg kg^-1 LPN for 30 days, respectively. LPN-H supplementation increased body length and femur length, improved femoral bone volume and microarchitecture, and upregulated osteoblast activity-related mRNA (<i>Bmp2</i>, <i>Smad8</i>, and <i>Runx-2</i>) expression in the femur. The content of secondary bile acid glycolithocholic acid (GLCA) in stool and serum was significantly increased after LPN-H intervention and positively correlated with the increased abundance of <i>Parabacteroides</i> in feces. In addition, the bile acid receptor FXR in femur was also activated in the LPN-H group, suggesting that LPN may regulate bone health through the microbiota-metabolite-bone axis. The results of this study suggest that LPN has potential application value in regulating bone metabolism during growth.