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Fecal Microbiomes in Premature Infants With and Without Parenteral Nutrition-Associated Cholestasis
Jasmeet S Mokha1, Zev H Davidovics1, Kendra Maas2
1Department of Pediatric Gastroenterology, Hepatology and Nutrition, Connecticut Children's Medical Center, University of Connecticut, Hartford.
Insights
Premature infants on parenteral nutrition (PN) who develop PN-associated cholestasis (PNAC) have distinct fecal microbiomes before diagnosis. These differences in gut bacteria may precede the onset of PNAC in vulnerable infants.
Area of Science:
- Neonatology
- Microbiome Research
- Gastroenterology
Background:
- Premature infants often require parenteral nutrition (PN) for growth.
- PN can lead to PN-associated cholestasis (PNAC), a serious complication.
- The role of the gut microbiome in PNAC development is not fully understood.
Purpose of the Study:
- To compare longitudinal changes in fecal microbiomes of premature infants who developed PNAC versus those who did not.
- To identify specific microbial differences preceding PNAC onset.
Main Methods:
- Analysis of 102 fecal samples from 8 premature infants with PNAC and 10 controls.
- Classification of samples into precholestasis, cholestasis, and postcholestasis based on bilirubin levels.
- Comparison of fecal microbiome composition using Nonmetric Multidimensional Scaling (NMDS) and indicator species analysis.
Main Results:
- Significant separation in fecal microbiome composition between cases and controls was observed early on.
- Precholestasis samples showed higher abundance of Firmicutes and Staphylococcus.
- Control samples were richer in Proteobacteria and Escherichia-Shigella; Bacilli were more prevalent in precholestasis.
- Microbiota differences largely resolved with PN weaning, except for increased diversity in controls post-resolution.
Conclusions:
- Premature neonates who develop PNAC exhibit significantly different fecal microbiomes compared to those who do not.
- These microbial alterations precede the biochemical detection of cholestasis.
- Fecal microbiome analysis may offer insights into PNAC pathogenesis and early detection.
Introduction:
Premature infants often require parenteral nutrition (PN) until they reach enteral autonomy which puts them at risk of developing PN-associated cholestasis (PNAC). We sought to compare longitudinal changes in fecal microbiomes of premature infants who developed PNAC versus those who did not despite being on similar PN doses.
Methods:
Stool samples from premature infants (gestational age <30 weeks) who developed direct bilirubin ≥1.5 mg/dL while receiving PN were classified as precholestasis, cholestasis, or postcholestasis based on bilirubin levels at the time of sample acquisition and were compared to matched control groups 1, 2, and 3, respectively.
Results:
A total of 102 fecal samples from 8 cases and 10 controls were analyzed. Precholestasis samples were more abundant in phylum Firmicutes and genus Staphylococcus, whereas control 1 was more abundant in phylum Proteobacteria and genus Escherichia-Shigella. Nonmetric multidimensional scaling ordination plots based on the taxonomic composition of early fecal samples revealed significant separation between cases and controls. On indicator species analysis, genus Bacilli was more prevalent in samples from the precholestasis group, whereas genus Escherichia-Shigella was more prevalent in control 1. With feeding advances, weaning of PN and resolution of PNAC, most differences in microbiota resolved with the exception of control 3 group being more diverse compared to the postcholestasis group.
Conclusions:
Premature neonates who develop PNAC, compared to those who do not, show significantly different fecal microbiomes preceding the biochemical detection of cholestasis.
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