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


Adams, LA and Wang, Z and Liddle, C and Melton, PE and Ariff, A and Chandraratna, H and Tan, J and Ching, H and Coulter, S and de Boer, B and Christophersen, CT and O'Sullivan, TA and Morrison, M and Jeffrey, GP, Bile acids associate with specific gut microbiota, low level alcohol consumption and liver fibrosis in patients with non-alcoholic fatty liver disease, Liver International, 40, (6) pp. 1356-1365. ISSN 1478-3223 (2020) [Refereed Article]

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Copyright 2020 John Wiley & Sons A/S. This is the peer reviewed version of the following article, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

DOI: doi:10.1111/liv.14453


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 between 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 BA's including glycocholic acid [GCA] and secondary conjugated BA's. In contrast, faecal BA increase was driven by secondary unconjugated BA's (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.

Item Details

Item Type:Refereed Article
Keywords:non-alcoholic steatohepatitis, fibrosis, microbiome, deoxycholic acid, diet
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Gastroenterology and hepatology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Melton, PE (Dr Phillip Melton)
ID Code:138404
Year Published:2020
Web of Science® Times Cited:18
Deposited By:Menzies Institute for Medical Research
Deposited On:2020-04-06
Last Modified:2020-08-07
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