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Extrahepatic Bile Duct and Gall Bladder Dissection in Nine-Day-Old Mouse Neonates
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Maternal regulation of biliary disease in neonates via gut microbial metabolites

Jai Junbae Jee1,2, Li Yang1, Pranavkumar Shivakumar1,3

  • 1Divisions of Gastroenterology, Hepatology and Nutrition and The Liver Care Center at Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

Nature Communications
|January 11, 2022
PubMed

Insights

Maternal butyrate intake protects newborns from biliary atresia by altering gut bacteria and metabolites. This finding offers potential therapeutic strategies for this severe neonatal liver disease.

Area of Science:

  • Microbiome research
  • Neonatal immunology
  • Gastroenterology

Background:

  • Maternal microbiome seeding influences neonatal health.
  • The impact on early-life disease susceptibility is unclear.
  • Biliary atresia is a severe neonatal cholangiopathy with unknown causes.

Purpose of the Study:

  • To investigate if maternal butyrate supplementation affects neonatal susceptibility to biliary atresia.
  • To identify microbial and metabolic changes associated with this protective effect.
  • To explore therapeutic potential of butyrate and glutamine in biliary atresia.

Main Methods:

  • Mice were fed butyrate during pregnancy.
  • Neonatal susceptibility to experimental biliary atresia was assessed.
  • Fecal microbiome and metabolome analyses were performed.
  • Butyrate and glutamine were administered to newborn mice.

Main Results:

  • Maternal butyrate reduced biliary atresia, inflammation, and injury in neonates.
  • Protection correlated with increased Bacteroidetes/Clostridia and altered glutamate/glutamine and hypoxanthine metabolites.
  • Human neonates with biliary atresia showed depleted beneficial bacteria and altered metabolite pathways.
  • Butyrate or glutamine administration attenuated disease in mice; glutamine enhanced bile duct cell survival.

Conclusions:

  • Maternal butyrate intake modulates the neonatal microbiome and metabolites, influencing experimental biliary atresia.
  • Specific microbial signatures and metabolic pathways are linked to disease protection.
  • Glutamine plays a role in protecting bile duct epithelial cells from cytotoxicity.

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