Bile acids associate with specific gut microbiota, low-level alcohol consumption and liver fibrosis in patients with non-alcoholic fatty liver disease

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Background: Bile acids (BAs) are synthesized by the liver and modified by gut bacteria, and may play an intermediary role between the gut microbiome and liver in promoting fibrosis in non-alcoholic fatty liver disease (NAFL...

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Main Authors: Adams, L.A., Wang, Z., Liddle, C., Melton, Phillip E., Ariff, A., Chandraratna, H., Tan, J., Ching, H., Coulter, S., de Boer, B., Christophersen, Claus, O’Sullivan, T.A., Morrison, M., Jeffrey, G.P.
Format: Journal Article
Language:English
Published: WILEY 2020
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/79136
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author Adams, L.A.
Wang, Z.
Liddle, C.
Melton, Phillip E.
Ariff, A.
Chandraratna, H.
Tan, J.
Ching, H.
Coulter, S.
de Boer, B.
Christophersen, Claus
O’Sullivan, T.A.
Morrison, M.
Jeffrey, G.P.
author_facet Adams, L.A.
Wang, Z.
Liddle, C.
Melton, Phillip E.
Ariff, A.
Chandraratna, H.
Tan, J.
Ching, H.
Coulter, S.
de Boer, B.
Christophersen, Claus
O’Sullivan, T.A.
Morrison, M.
Jeffrey, G.P.
author_sort Adams, L.A.
building Curtin Institutional Repository
collection Online Access
description © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Background: Bile acids (BAs) are synthesized by the liver and modified by gut bacteria, and may play an intermediary role between the gut microbiome and liver in promoting fibrosis in non-alcoholic fatty liver disease (NAFLD). We investigated the associations between serum and faecal BAs, gut microbiome and fibrosis in patients with and without NAFLD and examined the impact of diet and alcohol consumption on these relationships. Methods: Adult patients (n = 122) underwent liver biopsy and BAs characterization by high-performance liquid chromatography/mass spectrometry. Gut microbiome composition was analysed using next-generation 16S rRNA sequencing. Diet and alcohol intake were determined by 3-day food diary. Results: Serum and faecal BA concentrations increased progressively among non-NAFLD controls (n = 55), NAFLD patients with no/mild fibrosis (F0-2, n = 58) and NAFLD with advanced fibrosis (F3/4, n = 9). Progressive increases in serum BAs were driven by primary conjugated BAs including glycocholic acid [GCA] and secondary conjugated BAs. In contrast, faecal BA increase was driven by secondary unconjugated BAs (predominately deoxycholic acid [DCA]). Serum GCA levels and faecal DCA levels correlated with the abundance of Bacteroidaceae and Lachnospiraceae, and stool secondary BAs with an unclassifiable family of the order Bacteroidales (Bacteroidales;other). These bacterial taxa were also associated with advanced fibrosis. Modest alcohol consumption was positively correlated with faecal DCA levels and relative abundance of Lachnospiracaea and Bacteroidales;other. Conclusions: Higher serum and faecal BA levels are associated with advanced fibrosis in NAFLD. Specific gut bacteria link alterations in BA profiles and advanced fibrosis, and may be influenced by low-level alcohol consumption.
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spelling curtin-20.500.11937-791362020-07-29T02:53:30Z Bile acids associate with specific gut microbiota, low-level alcohol consumption and liver fibrosis in patients with non-alcoholic fatty liver disease Adams, L.A. Wang, Z. Liddle, C. Melton, Phillip E. Ariff, A. Chandraratna, H. Tan, J. Ching, H. Coulter, S. de Boer, B. Christophersen, Claus O’Sullivan, T.A. Morrison, M. Jeffrey, G.P. Science & Technology Life Sciences & Biomedicine Gastroenterology & Hepatology deoxycholic acid diet fibrosis microbiome non-alcoholic steatohepatitis FARNESOID X RECEPTOR STEATOHEPATITIS INFLAMMATION MODULATION MECHANISM PROFILE NASH TERM © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Background: Bile acids (BAs) are synthesized by the liver and modified by gut bacteria, and may play an intermediary role between the gut microbiome and liver in promoting fibrosis in non-alcoholic fatty liver disease (NAFLD). We investigated the associations between serum and faecal BAs, gut microbiome and fibrosis in patients with and without NAFLD and examined the impact of diet and alcohol consumption on these relationships. Methods: Adult patients (n = 122) underwent liver biopsy and BAs characterization by high-performance liquid chromatography/mass spectrometry. Gut microbiome composition was analysed using next-generation 16S rRNA sequencing. Diet and alcohol intake were determined by 3-day food diary. Results: Serum and faecal BA concentrations increased progressively among non-NAFLD controls (n = 55), NAFLD patients with no/mild fibrosis (F0-2, n = 58) and NAFLD with advanced fibrosis (F3/4, n = 9). Progressive increases in serum BAs were driven by primary conjugated BAs including glycocholic acid [GCA] and secondary conjugated BAs. In contrast, faecal BA increase was driven by secondary unconjugated BAs (predominately deoxycholic acid [DCA]). Serum GCA levels and faecal DCA levels correlated with the abundance of Bacteroidaceae and Lachnospiraceae, and stool secondary BAs with an unclassifiable family of the order Bacteroidales (Bacteroidales;other). These bacterial taxa were also associated with advanced fibrosis. Modest alcohol consumption was positively correlated with faecal DCA levels and relative abundance of Lachnospiracaea and Bacteroidales;other. Conclusions: Higher serum and faecal BA levels are associated with advanced fibrosis in NAFLD. Specific gut bacteria link alterations in BA profiles and advanced fibrosis, and may be influenced by low-level alcohol consumption. 2020 Journal Article http://hdl.handle.net/20.500.11937/79136 10.1111/liv.14453 English WILEY restricted
spellingShingle Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
deoxycholic acid
diet
fibrosis
microbiome
non-alcoholic steatohepatitis
FARNESOID X RECEPTOR
STEATOHEPATITIS
INFLAMMATION
MODULATION
MECHANISM
PROFILE
NASH
TERM
Adams, L.A.
Wang, Z.
Liddle, C.
Melton, Phillip E.
Ariff, A.
Chandraratna, H.
Tan, J.
Ching, H.
Coulter, S.
de Boer, B.
Christophersen, Claus
O’Sullivan, T.A.
Morrison, M.
Jeffrey, G.P.
Bile acids associate with specific gut microbiota, low-level alcohol consumption and liver fibrosis in patients with non-alcoholic fatty liver disease
title Bile acids associate with specific gut microbiota, low-level alcohol consumption and liver fibrosis in patients with non-alcoholic fatty liver disease
title_full Bile acids associate with specific gut microbiota, low-level alcohol consumption and liver fibrosis in patients with non-alcoholic fatty liver disease
title_fullStr Bile acids associate with specific gut microbiota, low-level alcohol consumption and liver fibrosis in patients with non-alcoholic fatty liver disease
title_full_unstemmed Bile acids associate with specific gut microbiota, low-level alcohol consumption and liver fibrosis in patients with non-alcoholic fatty liver disease
title_short Bile acids associate with specific gut microbiota, low-level alcohol consumption and liver fibrosis in patients with non-alcoholic fatty liver disease
title_sort bile acids associate with specific gut microbiota, low-level alcohol consumption and liver fibrosis in patients with non-alcoholic fatty liver disease
topic Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
deoxycholic acid
diet
fibrosis
microbiome
non-alcoholic steatohepatitis
FARNESOID X RECEPTOR
STEATOHEPATITIS
INFLAMMATION
MODULATION
MECHANISM
PROFILE
NASH
TERM
url http://hdl.handle.net/20.500.11937/79136