Maternal regulation of biliary disease in neonates via gut microbial metabolites

Jai Junbae Jee, Li Yang, Pranavkumar Shivakumar, Pei pei Xu, Reena Mourya, Unmesha Thanekar, Pu Yu, Yu Zhu, Yongkang Pan, Haibin Wang, Xufei Duan, Yongqin Ye, Bin Wang, Zhu Jin, Yuanmei Liu, Zhiqing Cao, Miki Watanabe-Chailland, Lindsey E. Romick-Rosendale, Michael Wagner, Lin FeiZhenhua Luo, Nicholas J. Ollberding, Shao tao Tang, Jorge A. Bezerra

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Maternal seeding of the microbiome in neonates promotes a long-lasting biological footprint, but how it impacts disease susceptibility in early life remains unknown. We hypothesized that feeding butyrate to pregnant mice influences the newborn’s susceptibility to biliary atresia, a severe cholangiopathy of neonates. Here, we show that butyrate administration to mothers renders newborn mice resistant to inflammation and injury of bile ducts and improves survival. The prevention of hepatic immune cell activation and survival trait is linked to fecal signatures of Bacteroidetes and Clostridia and increases glutamate/glutamine and hypoxanthine in stool metabolites of newborn mice. In human neonates with biliary atresia, the fecal microbiome signature of these bacteria is under-represented, with suppression of glutamate/glutamine and increased hypoxanthine pathways. The direct administration of butyrate or glutamine to newborn mice attenuates the disease phenotype, but only glutamine renders bile duct epithelial cells resistant to cytotoxicity by natural killer cells. Thus, maternal intake of butyrate influences the fecal microbial population and metabolites in newborn mice and the phenotypic expression of experimental biliary atresia, with glutamine promoting survival of bile duct epithelial cells.

Original languageEnglish (US)
Article number18
JournalNature communications
Issue number1
StatePublished - Dec 2022
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • General
  • Physics and Astronomy(all)


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