How a breast milk sugar supports infant gut development and prevents jaundice

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by Miles Martin, University of California - San Diego

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Human breast milk contains many bioactive compounds, but there are still many unanswered questions about their role in infant metabolism and development. New UC San Diego research suggests that a sugar found in breast milk could play a major role in intestinal development and prevent infant jaundice, a common condition in newborns. Credit: Erik Jepsen/UC San Diego

A new study by researchers at the University of California San Diego School of Medicine sheds light on the role of breast milk in supporting intestinal development and preventing hyperbilirubinemia, a condition in which bilirubin, a waste product from broken-down red blood cells, builds up in the blood and causes yellowing of the skin and eyes known as jaundice.

In an animal model of neonatal hyperbilirubinemia, the scientists discovered that a sugar found in breast milk called 3'-sialyllactose (3'SL) supports intestinal cell maturation and bilirubin processing. The researchers found that losing this sugar disrupts cellular signaling and maturation, highlighting a potential long-term role in gut health.

Breast milk's complex role in jaundice

Neonatal hyperbilirubinemia, commonly known as infant jaundice, affects up to 60% of term infants and 80% of preterm infants. In most cases, the disease is mild and goes away on its own, but when bilirubin rises too high or persists too long, it can cross the blood-brain barrier and lead to long-term neurological consequences.

Breastfed infants can also develop prolonged unconjugated hyperbilirubinemia, often referred to as breast milk jaundice. Breast milk jaundice is thought to be caused by a combination of slower milk intake in the first days of life and factors related to milk composition. However, scientists are still working to understand how bioactive components of breast milk influence bilirubin metabolism.

Milk sugar linked to gut resilience

To explore these questions, the researchers worked with scientists at UC San Diego's Human Milk Institute to analyze the gut-health effects of specific sugars found in breast milk. Studying mice, the team found:

  • Mouse pups fed on milk without 3'SL had lower survival, poorer growth, shorter intestines and more severe jaundice. Intestinal levels of the enzyme UGT1A1, which helps clear bilirubin, were markedly reduced.
  • These mice also showed different patterns of gene expression, including reduced markers of cellular maturation.
  • Loss of St3gal4, a gene linked to 3'SL availability, was associated with abnormal activation of pancreatic genes in the pups.
  • Mice with persistent St3gal4 deficiency were also more vulnerable to chemically induced colon injury as adults, showing greater weight loss and lower survival.

"Our results suggest that early milk exposure could have lasting, systemic impacts on gut resilience," said senior study author Robert Tukey, Ph.D., distinguished professor of pharmacology at UC San Diego School of Medicine. "Our research also suggests that natural differences in milk sugar composition could help explain why some infants develop more severe jaundice than others. This raises the possibility of nutritional strategies that could help support intestinal maturation and prevent jaundice."

The paper is published in the journal Cellular and Molecular Gastroenterology and Hepatology.

More information

Xiaojing Yang et al., Maternal Milk 3′-Sialyllactose Promotes Neonatal Intestinal Maturation and Prevents Hyperbilirubinemia through an HNF4α-Associated Pathway, Cellular and Molecular Gastroenterology and Hepatology (2026). DOI: 10.1016/j.jcmgh.2026.101924

Key medical concepts

Hyperbilirubinemia, Neonatal

Clinical categories

PediatricsChildren's healthGastroenterologyCommon illnesses & Prevention Provided by University of California - San Diego Who's behind this story?

Robert Egan

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