Lactopontin regulates gut microbiota and calcium absorption to promote bone growth in growing rats

Lactopontin (LPN) is an important milk protein with the potential to improve bone health, however, the specific effects have not been determined. This study investigates the effects of LPN on early bone growth and development. 3-week-old SD rats (n = 16) were assigned to the control group and LPN group, receiving intragastric administration of deionized water and 15 mg/kg LPN for 30 days respectively. LPN supplementation increased body length, femur length and femur strength, improved femoral bone volume and microarchitecture, and upregulated the expression of osteoblast activity related mRNA (Bmp2, Smad8, Wnt10b and β-catenin) in the femur. The abundance of Parabacteroides in feces and the content of glycochenodeoxycholic acid (GCDCA) in serum were significantly elevated following LPN intervention. Additionally, the bile acid receptor TGR5 in the femur was activated in the LPN group, suggesting that LPN may regulate bone health via the microbiota-metabolites-bone axis. Furthermore, LPN promoted calcium absorption through transcellular and cellular bypass pathways, resulting in a significant increase in serum calcium content. These results indicate that LPN has potential application value in regulating bone metabolism during growth.