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Significance The benefits of breast milk in neonatal development are well characterized. However, very little is known about the essential nutrient components in breast milk that are critical for neonatal development and how these nutrients are maintained at adequate levels in breast milk. The present work demonstrates that the intestine is an essential sensor of systemic iron demand during lactation. During high iron demand from lactation, hypoxia-inducible factor-2α–mediated increase in maternal intestinal iron absorption is essential to maintain milk iron levels. This work demonstrates the significant role of maternal intestinal iron absorption in postnatal iron homeostasis of newborns and provides a therapeutic target to maintain iron homeostasis during pregnancy and lactation in anemic patients who are refractory to iron supplementation.

Maternal intestinal HIF-2α is necessary for sensing iron demands of lactation in mice