The metabolic changes that occur during the postnatal weaning period appear to be particularly important for future health, and human breast milk is considered to provide the optimal source of nutrition for infants. Our previous studies examined the effect of feeding type on antioxidative properties, glucose and insulin metabolism, the lipid profile, metabolomics, and prostaglandin (PG) metabolism in term and preterm infants. A urinary marker of oxidative DNA damage (8‐hydroxy‐2′‐deoxyguanosine) was significantly lower in breast‐fed term and preterm infants than in formula‐fed infants. Markers of insulin sensitivity were significantly lower and atherosclerotic indices were significantly higher in breast‐fed preterm infants than in mixed‐fed infants at discharge. On urinary metabolomics analysis, choline, choline metabolites, and lactic acid were significantly lower in breast‐fed term infants than in formula‐fed infants. Urinary PGD₂ metabolite level in breast‐fed term infants was also significantly lower than in formula‐fed term infants. This indicates that human breast milk affects biological metabolism in early infancy.

Chronic enteropathy associated withSLCO2A1gene (CEAS) is caused by loss-of-function mutations inSLCO2A1, which encodes a prostaglandin (PG) transporter. In this study, we report a sibling case of CEAS with a novel pathogenic variant of theSLCO2A1gene. Compound heterozygous variants inSLCO2A1were identified in an 8-year-old boy and 12-year-old girl, and multiple chronic nonspecific ulcers were observed in the patients using capsule endoscopy. The splice site mutation (c.940 + 1G>A) of the paternal allele was previously reported to be pathogenic, whereas the missense variant (c.1688T>C) of the maternal allele was novel and had not yet been reported. The affected residue (p.Leu563Pro) is located in the 11th transmembrane domain (helix 11) of SLCO2A1. Because SLCO2A1 mediates the uptake and clearance of PGs, the urinary PG metabolites were measured by liquid chromatography coupled to tandem mass spectrometry. The urinary tetranor-prostaglandin E metabolite levels in the patients were significantly higher than those in unaffected individuals. We established cell lines with doxycycline-inducible expression of wild type SLCO2A1 (WT-SLCO2A1) and the L563P mutant. Immunofluorescence staining showed that WT-SLCO2A1 and the L563P mutant were dominantly expressed on the plasma membranes of these cells. Cells expressing WT-SLCO2A1 exhibited time- and dose-dependent uptake of PGE₂, while the mutant did not show any uptake activity. Residue L563 is very close to the putative substrate-binding site in SLCO2A1, R561 in helix 11. However, in a molecular model of SLCO2A1, the side chain of L563 projected outside of helix 11, indicating that L563 is likely not directly involved in substrate binding. Instead, the substitution of Pro may twist the helix and impair the transporter function. In summary, we identified a novel pathogenic variant ofSLCO2A1that caused loss-of-function and induced CEAS.