Alterations in gut microbial function following liver transplant

Jasmohan S. Bajaj; Genta Kakiyama; I. Jane Cox; Hiroshi Nittono; Hajime Takei; Melanie White; Andrew Fagan; Edith A. Gavis; Douglas M. Heuman; Ho Chong Gilles; Phillip Hylemon; Simon D. Taylor-Robinson; Cristina Legido-Quigley; Min Kim; Jin Xu; Roger Williams; Masoumeh Sikaroodi; William M. Pandak; Patrick M. Gillevet

doi:10.1002/lt.25046

Alterations in gut microbial function following liver transplant

Jasmohan S. Bajaj^*, Genta Kakiyama, I. Jane Cox, Hiroshi Nittono, Hajime Takei, Melanie White, Andrew Fagan, Edith A. Gavis, Douglas M. Heuman, Ho Chong Gilles, Phillip Hylemon, Simon D. Taylor-Robinson, Cristina Legido-Quigley, Min Kim, Jin Xu, Roger Williams, Masoumeh Sikaroodi, William M. Pandak, Patrick M. Gillevet

^*Corresponding author for this work

Institute of Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

68 Citations (Scopus)

Abstract

Liver transplantation (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. The aims were to determine the effect of LT on gut microbial functionality focusing on endotoxemia, bile acid (BA), ammonia metabolism, and lipidomics. We enrolled outpatient patients with cirrhosis on the LT list and followed them until 6 months after 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. We enrolled 40 patients (age, 56 ± 7 years; mean Model for End-Stage Liver Disease score, 22.6). They received LT 6 ± 3 months after enrollment and were re-evaluated 7 ± 3 months after 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 after LT compared with baseline. Stool BAs increased significantly after LT, and there was evidence of greater bacterial action (higher secondary, oxo and iso-BAs) after LT although the levels of conjugated BAs remained similar. There was a reduced serum ammonia and corresponding rise in urinary phenylacetylglutamine after LT. There was an increase in urinary trimethylamine-N-oxide, which was correlated with specific changes in serum lipids related to cell membrane products. The ultimate post-LT lipidomic profile appeared beneficial compared with the profile before LT. In conclusion, LT improves gut microbiota diversity and dysbiosis, which is accompanied by favorable changes in gut microbial functionality corresponding to BAs, ammonia, endotoxemia, lipidomic, and metabolomic profiles. Liver Transplantation 24 752–761 2018 AASLD.

Original language	English
Pages (from-to)	752-761
Number of pages	10
Journal	Liver Transplantation
Volume	24
Issue number	6
Early online date	13 May 2018
DOIs	https://doi.org/10.1002/lt.25046
Publication status	Published - 1 Jun 2018

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Bajaj, J. S., Kakiyama, G., Cox, I. J., Nittono, H., Takei, H., White, M., Fagan, A., Gavis, E. A., Heuman, D. M., Gilles, H. C., Hylemon, P., Taylor-Robinson, S. D., Legido-Quigley, C., Kim, M., Xu, J., Williams, R., Sikaroodi, M., Pandak, W. M., & Gillevet, P. M. (2018). Alterations in gut microbial function following liver transplant. Liver Transplantation, 24(6), 752-761. https://doi.org/10.1002/lt.25046

@article{9b62fb4c635c436297e4f79bcbf04261,

title = "Alterations in gut microbial function following liver transplant",

abstract = "Liver transplantation (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. The aims were to determine the effect of LT on gut microbial functionality focusing on endotoxemia, bile acid (BA), ammonia metabolism, and lipidomics. We enrolled outpatient patients with cirrhosis on the LT list and followed them until 6 months after 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. We enrolled 40 patients (age, 56 ± 7 years; mean Model for End-Stage Liver Disease score, 22.6). They received LT 6 ± 3 months after enrollment and were re-evaluated 7 ± 3 months after 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 after LT compared with baseline. Stool BAs increased significantly after LT, and there was evidence of greater bacterial action (higher secondary, oxo and iso-BAs) after LT although the levels of conjugated BAs remained similar. There was a reduced serum ammonia and corresponding rise in urinary phenylacetylglutamine after LT. There was an increase in urinary trimethylamine-N-oxide, which was correlated with specific changes in serum lipids related to cell membrane products. The ultimate post-LT lipidomic profile appeared beneficial compared with the profile before LT. In conclusion, LT improves gut microbiota diversity and dysbiosis, which is accompanied by favorable changes in gut microbial functionality corresponding to BAs, ammonia, endotoxemia, lipidomic, and metabolomic profiles. Liver Transplantation 24 752–761 2018 AASLD.",

author = "Bajaj, {Jasmohan S.} and Genta Kakiyama and Cox, {I. Jane} and Hiroshi Nittono and Hajime Takei and Melanie White and Andrew Fagan and Gavis, {Edith A.} and Heuman, {Douglas M.} and Gilles, {Ho Chong} and Phillip Hylemon and Taylor-Robinson, {Simon D.} and Cristina Legido-Quigley and Min Kim and Jin Xu and Roger Williams and Masoumeh Sikaroodi and Pandak, {William M.} and Gillevet, {Patrick M.}",

year = "2018",

month = jun,

day = "1",

doi = "10.1002/lt.25046",

language = "English",

volume = "24",

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journal = "Liver Transplantation",

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Bajaj, JS, Kakiyama, G, Cox, IJ, Nittono, H, Takei, H, White, M, Fagan, A, Gavis, EA, Heuman, DM, Gilles, HC, Hylemon, P, Taylor-Robinson, SD, Legido-Quigley, C , Kim, M , Xu, J, Williams, R, Sikaroodi, M, Pandak, WM & Gillevet, PM 2018, 'Alterations in gut microbial function following liver transplant', Liver Transplantation, vol. 24, no. 6, pp. 752-761. https://doi.org/10.1002/lt.25046

TY - JOUR

T1 - Alterations in gut microbial function following liver transplant

AU - Bajaj, Jasmohan S.

AU - Kakiyama, Genta

AU - Cox, I. Jane

AU - Nittono, Hiroshi

AU - Takei, Hajime

AU - White, Melanie

AU - Fagan, Andrew

AU - Gavis, Edith A.

AU - Heuman, Douglas M.

AU - Gilles, Ho Chong

AU - Hylemon, Phillip

AU - Taylor-Robinson, Simon D.

AU - Legido-Quigley, Cristina

AU - Kim, Min

AU - Xu, Jin

AU - Williams, Roger

AU - Sikaroodi, Masoumeh

AU - Pandak, William M.

AU - Gillevet, Patrick M.

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Liver transplantation (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. The aims were to determine the effect of LT on gut microbial functionality focusing on endotoxemia, bile acid (BA), ammonia metabolism, and lipidomics. We enrolled outpatient patients with cirrhosis on the LT list and followed them until 6 months after 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. We enrolled 40 patients (age, 56 ± 7 years; mean Model for End-Stage Liver Disease score, 22.6). They received LT 6 ± 3 months after enrollment and were re-evaluated 7 ± 3 months after 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 after LT compared with baseline. Stool BAs increased significantly after LT, and there was evidence of greater bacterial action (higher secondary, oxo and iso-BAs) after LT although the levels of conjugated BAs remained similar. There was a reduced serum ammonia and corresponding rise in urinary phenylacetylglutamine after LT. There was an increase in urinary trimethylamine-N-oxide, which was correlated with specific changes in serum lipids related to cell membrane products. The ultimate post-LT lipidomic profile appeared beneficial compared with the profile before LT. In conclusion, LT improves gut microbiota diversity and dysbiosis, which is accompanied by favorable changes in gut microbial functionality corresponding to BAs, ammonia, endotoxemia, lipidomic, and metabolomic profiles. Liver Transplantation 24 752–761 2018 AASLD.

AB - Liver transplantation (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. The aims were to determine the effect of LT on gut microbial functionality focusing on endotoxemia, bile acid (BA), ammonia metabolism, and lipidomics. We enrolled outpatient patients with cirrhosis on the LT list and followed them until 6 months after 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. We enrolled 40 patients (age, 56 ± 7 years; mean Model for End-Stage Liver Disease score, 22.6). They received LT 6 ± 3 months after enrollment and were re-evaluated 7 ± 3 months after 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 after LT compared with baseline. Stool BAs increased significantly after LT, and there was evidence of greater bacterial action (higher secondary, oxo and iso-BAs) after LT although the levels of conjugated BAs remained similar. There was a reduced serum ammonia and corresponding rise in urinary phenylacetylglutamine after LT. There was an increase in urinary trimethylamine-N-oxide, which was correlated with specific changes in serum lipids related to cell membrane products. The ultimate post-LT lipidomic profile appeared beneficial compared with the profile before LT. In conclusion, LT improves gut microbiota diversity and dysbiosis, which is accompanied by favorable changes in gut microbial functionality corresponding to BAs, ammonia, endotoxemia, lipidomic, and metabolomic profiles. Liver Transplantation 24 752–761 2018 AASLD.

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U2 - 10.1002/lt.25046

DO - 10.1002/lt.25046

M3 - Article

AN - SCOPUS:85048346028

SN - 1527-6465

VL - 24

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EP - 761

JO - Liver Transplantation

JF - Liver Transplantation

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ER -

Alterations in gut microbial function following liver transplant

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