Abstract:The objective of this study was to elucidate the differential absorption and underlying mechanisms of lactoferrin isolated from human milk, goat milk, and cow milk in the intestines of young infants. Employing fluorescent labeling techniques, we tracked the intestinal distribution of lactoferrin in live mice, revealing that lactoferrin exhibited substantial resistance to gastrointestinal digestion and distribution within the intestinal tract, with detectable fluorescence signals persisting up to 8 hours post-gastric administration. Human lactoferrin, purified using ultrafiltration technology, achieved a purity level exceeding 90%, which is suitable for further experimental use. Ussing Chamber experiments indicated that goat lactoferrin showed a higher intestinal absorption efficiency of 90.15 μg, which was closer to the absorption efficiency of human lactoferrin, 145.0 μg. Further mechanistic investigations revealed that goat lactoferrin significantly up-regulated the expression of the Itln-1 gene in the proximal jejunum (P<0.05), an effect comparable to human lactoferrin. Moreover, goat lactoferrin uniquely up-regulated the expression of the Lrp-1 gene in the proximal jejunum and the Itln-1 gene in the proximal ileum, effects not observed with human and bovine lactoferrin treatments. These findings imply that goat lactoferrin may enhance its intestinal absorption efficiency by modulating the expression of specific membrane receptors, thereby promoting the endocytic pathway. Collectively, this study uncovers the potential absorptive advantages of goat lactoferrin and offers molecular insights into the nutritional benefits of goat milk, potentially informing the design and refinement of infant formula formulations.