Parenteral Lipids Shape Gut Bile Acid Pools and Microbiota Profiles in the Prevention of Cholestasis in Preterm Pigs

Authors

Lee Call
Tiffany Molina
Barbara Stoll
Greg Guthrie
Shaji Chacko
Jogchum Plat
Jason Robinson
Sen Lin
Caitlin Vonderohe
Mahmoud Mohammad
Dennis Kunichoff
Stephanie Cruz
Patricio Lau
Muralidhar Premkumar
Jon Nielsen
Zhengfeng Fang
Oluyinka Olutoye
Thomas Thymann
Robert Britton
Per Sangild
Douglas Burrin

Publication Date

7-1-2020

Journal

Journal of Lipid Research

DOI

10.1194/jlr.RA120000652

PMID

32350078

PMCID

PMC7328048

PubMedCentral® Posted Date

4-29-2020

PubMedCentral® Full Text Version

Post-print

Published Open-Access

no

Keywords

Animals, Bile Acids and Salts, Cholestasis, Lipid Metabolism, Microbiota, Parenteral Nutrition, Premature Birth, Swine, liver, cholestasis, parenteral nutrition, sterols, fatty acids, metabolomics, microbiome, clostridium, Enterobacteriaceae

Abstract

Multi-component lipid emulsions, rather than soy-oil emulsions, prevent cholestasis by an unknown mechanism. Here, we quantified liver function, bile acid pools, and gut microbial and metabolite profiles in premature parenterally fed pigs given a soy-oil lipid emulsion, Intralipid (IL), a multi component lipid emulsion, SMOFlipid (SMOF), a novel emulsion with a modified fatty-acid composition [experimental emulsion (EXP)], or a control enteral diet (ENT) for 22 days. We assayed serum cholestasis markers, measured total bile acid levels in plasma, liver, and gut contents, and analyzed colonic bacterial 16S rRNA gene sequences and metabolomic profiles. Serum cholestasis markers (i.e., bilirubin, bile acids, and γ-glutamyl transferase) were highest in IL-fed pigs and normalized in those given SMOF, EXP, or ENT. Gut bile acid pools were lowest in the IL treatment and were increased in the SMOF and EXP treatments and comparable to ENT. Multiple bile acids, especially their conjugated forms, were higher in the colon contents of SMOF and EXP than in IL pigs. The colonic microbial communities of SMOF and EXP pigs had lower relative abundance of several gram-positive anaerobes, including Clostridrium XIVa, and higher abundance of Enterobacteriaceae than those of IL and ENT pigs. Differences in lipid and microbial-derived compounds were also observed in colon metabolite profiles. These results indicate that multi-component lipid emulsions prevent cholestasis and restore enterohepatic bile flow in association with gut microbial and metabolomic changes. We conclude that sustained bile flow induced by multi-component lipid emulsions likely exerts a dominant effect in reducing bile acid-sensitive gram-positive bacteria.