Lactopontin in a Simulated Infant Formula Protein Matrix Promotes Bone Development via the Gut–Bone Axis in Growing Rats

BACKGROUND: Lactopontin (L-OPN) is a pivotal bioactive protein present in breast milk that supports bone development, but its efficacy in a formula matrix is unknown. This study aimed to evaluate the effects of L-OPN-fortified formula on bone growth in a growing rat model and to explore the underlying mechanisms. METHODS: = 8/group) received daily gavage for four weeks: (1) CON-deionized water; (2) PRO-750 mg/kg·BW mixed protein; or (3) L-OPN-750 mg/kg·BW of the PRO formula fortified with L-OPN. RESULTS: < 0.05). Metabolomic analysis revealed that L-OPN supplementation significantly altered bile acid metabolism, notably increasing serum levels of 12-ketolithocholic acid (12-KLCA), which correlated strongly with bone metrics. CONCLUSIONS: These preclinical findings provide a basis for future research in infant formula.