TY - JOUR
T1 - Parenteral lipids shape gut bile acid pools and microbiota profiles in the prevention of cholestasis in preterm pigs[S]
AU - Call, Lee
AU - Molina, Tiffany
AU - Stoll, Barbara
AU - Guthrie, Greg
AU - Chacko, Shaji
AU - Plat, Jogchum
AU - Robinson, Jason
AU - Lin, Sen
AU - Vonderohe, Caitlin
AU - Mohammad, Mahmoud
AU - Kunichoff, Dennis
AU - Cruz, Stephanie
AU - Lau, Patricio
AU - Premkumar, Muralidhar
AU - Nielsen, Jon
AU - Fang, Zhengfeng
AU - Olutoye, Oluyinka
AU - Thymann, Thomas
AU - Britton, Robert
AU - Sangild, Per
AU - Burrin, Douglas
N1 - Funding Information:
Fresenius Kabi, the Whitlock Foundation, National Institutes of Health Grant DK-094616 (D.G.B), and the
Funding Information:
This work was supported in part by federal funds from the USDA, Agricultural Research Service under
Funding Information:
We wish to thank the veterinarians and animal care attendants from Baylor College of Medicine’s Center for Comparative Medicine for their assistance with animal housing and care in support of this study. This work was supported in part by federal funds from the USDA, Agricultural Research Service under Cooperative Agreement Number 3092-51000-060-01, and grants from the University of Copenhagen, Fresenius Kabi, the Whitlock Foundation, National Institutes of Health Grant DK-094616 (D.G.B), and the Texas Medical Center Digestive Diseases Center (NIH Grant P30 DK-56338). Lee Call was supported by training fellowships from the National Institutes of Health Grant T32-GM088129 and Gulf Coast Consortia, NLM Training Program in Biomedical Informatics (T15-LM007093).
Funding Information:
Cooperative Agreement Number 3092-51000-060-01, and grants from the University of Copenhagen,
Publisher Copyright:
© 2020 American Society for Biochemistry and Molecular Biology Inc.. All rights reserved.
PY - 2020/7
Y1 - 2020/7
N2 - 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 gamma-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, includingClostridriumXIVa, 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.
AB - 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 gamma-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, includingClostridriumXIVa, 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.
KW - liver
KW - cholestasis
KW - parenteral nutrition
KW - sterols
KW - fatty acids
KW - metabolomics
KW - microbiome
KW - clostridium
KW - Enterobacteriaceae
KW - NUTRITION-ASSOCIATED CHOLESTASIS
KW - RANDOMIZED CONTROLLED-TRIAL
KW - LIVER-DISEASE
KW - FISH-OIL
KW - DEVELOPMENTAL PATTERN
KW - CHILDREN
KW - EMULSIONS
KW - INFANTS
KW - METABOLISM
KW - TERM
U2 - 10.1194/jlr.RA120000652
DO - 10.1194/jlr.RA120000652
M3 - Article
C2 - 32350078
SN - 0022-2275
VL - 61
SP - 1038
EP - 1051
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 7
ER -