Alterations in gut microbial function following liver transplant
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Liver transplant (LT) improves daily function and ameliorates gut microbial composition. However, the effect of LT on microbial functionality, which can be related to overall patient benefit, is unclear and could affect the post-LT course. AIMS: To determine the effect of LT on gut microbial functionality focusing on endotoxemia, bile acid (BA), ammonia metabolism and lipidomics. METHOD: We enrolled outpatient cirrhotic patients on the LT list and followed them till 6 months post-LT. Microbiota composition (Shannon diversity and individual taxa) and function analysis (serum endotoxin, urinary metabolomics and serum lipidomics, and stool BA profile) and cognitive tests were performed at both visits. RESULTS: We enrolled 40 patients (56±7 years, MELD 23). They received LT 6±3 months after enrollment and were re-evaluated 7±3 months post-LT with a stable course. A significant improvement in cognition with increase in microbial diversity, increase in autochthonous and decrease in potentially pathogenic taxa and reduced endotoxemia were seen post-LT compared to baseline. Stool BAs increased significantly post-LT and there was evidence of greater bacterial action (higher secondary, oxo and iso-BAs) post-LT although the levels of conjugated BAs remained similar. There was a reduced serum ammonia and corresponding rise in urinary phenylacetylglutamine (PAG) post-LT. There was an increase in urinary trimethylamine-N-oxide (TMAO), which was correlated with specific changes in serum lipids related to cell membrane products. The ultimate post-LT lipidomic profile appeared beneficial compared to the pre-LT. CONCLUSIONS: LT improves gut microbiota diversity and dysbiosis which is accompanied by favorable changes in gut microbial functionality corresponding to bile acids, ammonia, endotoxemia, lipidomic and metabolomic profiles. This article is protected by copyright. All rights reserved.
Date Issued
2018-06-01
Date Acceptance
2018-02-25
Citation
Liver Transplantation and Surgery, 2018, 24 (6), pp.752-761
ISSN
1074-3022
Publisher
Wiley
Start Page
752
End Page
761
Journal / Book Title
Liver Transplantation and Surgery
Volume
24
Issue
6
Copyright Statement
© 2018 by the American Association for the Study of Liver Diseases. This is the accepted version of the following article, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/lt.25046/abstract
Sponsor
National Institutes of Health
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29500907
Grant Number
5R01AA020203-02
Subjects
Lipidomics
Trimethylamine-N-oxide
bile acids
endotoxin
metabolomics
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2018-03-03