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Published on: November 27, 2016
Fecal Microbiome and Bile Acid Profiles Differ in Preterm Infants with Parenteral Nutrition-associated Cholestasis
Ellen S Wagner1, Kaitlyn Oliphant1, Mark D'Souza1
1Department of Pediatrics, University of Chicago, Chicago, IL, USA.
Insights
Parenteral nutrition-associated cholestasis (PNAC) in premature infants is linked to gut microbiome and bile acid differences. Specific bacterial and bile acid profiles may predict or influence PNAC development.
Area of Science:
- Neonatalogy
- Microbiome Research
- Gastroenterology
Background:
- Parenteral nutrition-associated cholestasis (PNAC) is common in premature infants, but not all infants receiving parenteral nutrition (PN) develop it.
- Differences in gut microbiome and fecal bile acid composition may influence PNAC development in premature infants receiving PN and varying enteral feeds.
Purpose of the Study:
- To investigate the relationship between fecal microbiome, bile acid content, and the development of PNAC in premature infants on PN.
Main Methods:
- Collected serial bilirubin measurements and fecal samples from 22 preterm infants during NICU admission.
- Performed 16S rRNA gene sequencing and bile acid analysis on fecal samples.
- Utilized binomial regression, adjusting for postmenstrual age and feed amount, to assess microbiome and bile acid impact on PNAC.
Main Results:
- Cholestatic infants had higher PN and antibiotic exposure and longer NICU stays.
- Non-cholestatic infants showed higher microbiome richness, with distinct bacterial abundances (lower Bacteroidota, higher Proteobacteria and Fusobacteriota).
- Lower deoxycholic acid concentrations were observed in cholestatic infants; Akkermansia abundance increased with feed volume in non-cholestatic infants.
Conclusions:
- This study is the first to link PNAC susceptibility, microbiome, and fecal bile acids in preterm infants.
- Identified distinct microbiome and bile acid patterns associated with PNAC development.
- Findings may guide the development of targeted therapies for PNAC in vulnerable preterm infants.
Background And Aims:
Parenteral nutrition (PN)-associated cholestasis (PNAC) is frequently diagnosed in premature infants; however, not all PN-exposed infants develop PNAC. We propose that, in premature infants receiving PN and varying amounts of enteral feeds, differences in the gut microbiome and fecal bile acid content are associated with PNAC development. This study aimed to examine the fecal microbiome and bile acid content of premature infants on PN to determine if there is a relationship with the development of PNAC.
Methods:
Twenty-two preterm infants had serial bilirubin measurements and fecal samples collected during their neonatal intensive care unit admission. Fecal samples underwent 16S rRNA gene sequencing and bile acid analysis. Binomial regression, adjusting for postmenstrual age with feed amount as a moderator, was used to assess the impact of the fecal microbiome and bile acids on PNAC development.
Results:
Cholestatic patients (n = 11) had greater PN and antibiotic exposure (p = 0.020; p = 0.010) and longer neonatal intensive care unit stays (p = 0.0038) than non-cholestatic patients. Microbiome richness was higher in non-cholestatic infants (p < 2E-16), with no difference in β diversity (p = 1.0). Cholestatic infants had a significantly higher abundance of Proteobacteria and Fusobacteriota and a lower abundance of Bacteroidota (p < 2E-16). Akkermansia was abundant in all infants on low feeds; as feed volume increased, Akkermansia abundance significantly increased in non-cholestatic infants (p < 2E-16). Bile acid analysis demonstrated significantly lower deoxycholic acid concentrations in cholestatic infants (p < 2E-16). Metagenomic analysis revealed an increase in Proteobacteria requiring augmented stress responses in non-cholestatic infants.
Conclusions:
This is the first study to directly explore the relationship between PNAC susceptibility, the microbiome, and fecal bile acids in preterm infants. The microbiome and bile acid patterns identified here may inform the development of targeted therapeutics for this vulnerable population.
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