Cholestasis Impairs Gut Microbiota Development and Bile Salt Hydrolase Activity in Preterm Neonates

Authors

Lauren E Lynch
Amy B Hair
Krishnakant G Soni
Heeju Yang
Laura A Gollins
Monica Narvaez-Rivas
Kenneth D R Setchell
Geoffrey A Preidis

Publication Date

1-1-2023

Journal

Gut Microbes

DOI

10.1080/19490976.2023.2183690

PMID

36843227

PMCID

PMC9980517

PubMedCentral® Posted Date

2-26-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Infant, Newborn, Gastrointestinal Microbiome, Case-Control Studies, Infant, Premature, Cholestasis, Ursodeoxycholic Acid, Bile Acids and Salts, Microbiome, cholestasis, bile acids, neonate, growth, premature infant, ursodeoxycholic acid, bile salt hydrolase

Abstract

Cholestasis refers to impaired bile flow from the liver to the intestine. In neonates, cholestasis causes poor growth and may progress to liver failure and death. Normal bile flow requires an intact liver-gut-microbiome axis, whereby liver-derived primary bile acids are transformed into secondary bile acids. Microbial bile salt hydrolase (BSH) enzymes are responsible for the first step, deconjugating glycine- and taurine-conjugated primary bile acids. Cholestatic neonates often are treated with the potent choleretic bile acid ursodeoxycholic acid (UDCA), although interactions between UDCA, gut microbes, and other bile acids are poorly understood. To gain insight into how the liver-gut-microbiome axis develops in extreme prematurity and how cholestasis alters this maturation, we conducted a nested case-control study collecting 124 stool samples longitudinally from 24 preterm infants born at mean 27.2 ± 1.8 weeks gestation and 946 ± 249.6 g, half of whom developed physiologic cholestasis. Samples were analyzed by whole metagenomic sequencing,