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AimPhosphorus is a critical constituent of bone as a component of hydroxyapatite. Bone mineral content accrues rapidly early in life necessitating a positive phosphorus balance, which could be established by a combination of increased renal reabsorption and intestinal absorption. Intestinal absorption can occur via a transcellular pathway mediated by the apical sodium‐phosphate cotransporter, Slc34a2/NaPiIIb or via the paracellular pathway. We sought to determine how young mammals increase dietary phosphorus absorption from the small intestine to establish a positive phosphorus balance, a prerequisite for rapid bone growth.MethodsThe developmental expression profile of genes mediating phosphate absorption from the small intestine was determined in mice by qPCR and immunohistochemistry. Additionally, Ussing chamber studies were performed on small bowel of young (p7–p14) and older (8‐ to 17‐week‐old) mice to examine developmental changes in paracellular Pi permeability and transcellular Pi transport.ResultsBlood and urinary Pi levels were higher in young mice. Intestinal paracellular phosphate permeability of young mice was significantly increased relative to older mice across all intestinal segments. NaPiIIb expression was markedly increased in juvenile mice, in comparison to adult animals. Consistent with this, young mice had increased transcellular phosphate flux across the jejunum and ileum relative to older animals. Moreover, transcellular phosphate transport was attenuated by the NaPiIIb inhibitor NTX1942 in the jejunum and ileum of young mice.ConclusionOur results are consistent with young mice increasing phosphate absorption via increasing paracellular permeability and the NaPiIIb‐mediated transcellular pathway.

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Background Phosphate (Pi) is a multivalent ion involved in a multitude of physiological processes including the formation of hydroxyapatite, the core structural component of bone. Hydroxyapatite formation occurs rapidly early in mammalian development enabling a high rate of bone formation. In the small intestine Pi absorption can occur by a transcellular or passive paracellular pathway. Of note, paracellular ion flux is governed largely by a family of proteins known as claudins, which confer permeability to epithelia. In the kidney, Pi reabsorption occurs entirely through the transcellular route. Pathological perturbations in Pi absorption and reabsorption can result in impaired bone formation and mineralization. We therefore aimed to characterize the normal developmental progression of Pi handling in the gut and kidney to determine mechanisms by which the developing mammal establishes a positive Pi balance. Methods Gene expression was determined by real‐time PCR of wild‐type mice aged 1, 7 days, 14 and 28 days as well as 2, 3 and 6 months of age. Of note, mice were weaned at 22 days of age. To assess developmental changes in paracellular Pi permeability, small bowel segments were isolated from mice aged 9‐14 days old or 15‐17 weeks of age and Chloride‐Pi diffusion potentials assessed in Ussing chambers. Results The secondary sodium‐Pi transporters NaPiIIb in the intestine and NaPiIIa, NaPiIIc in the kidney all showed peak expression levels early in development and proceeded to decrease in their expression levels into adulthood. However, unlike NaPiIIb which consistently displayed high expression before weaning age, NaPiIIa and NaPiIIc expression showed a lifetime low during early suckling followed by maximum lifetime expression at 2 weeks of age. There were no specific changes in claudin expression throughout development. Consistent with this, paracellular Pi permeability did not change between 9‐14 days and 15‐17 months of age along the intestine. Discussion Our results suggest that the mechanism responsible for establishing a positive Pi balance in young mammals is via increased transcellular absorption/reabsorption, whereas paracellular Pi flux is unlikely a significant contributor.