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

Leon A Adams^{1

2}, Zhengyi Wang^{1

2}, Chris Liddle³, Phillip E Melton^{4

5}, Amir Ariff⁴, Harsha Chandraratna⁶, Jeremy Tan⁷, Helena Ching¹, Sally Coulter³, Bastiaan de Boer⁸, Claus T Christophersen^{9

10}, Therese A O'Sullivan⁹, Mark Morrison¹¹, Gary P Jeffrey^{1

2}

Affiliations

¹ Medical School, Faculty of Medical and Health Sciences, The University of Western Australia, Perth, WA, Australia.
² Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
³ Storr Liver Centre, The Westmead Institute, University of Sydney, Westmead, NSW, Australia.
⁴ Curtin/UWA Centre for Genetic Origins of Health and Disease, Curtin University and University of Western Australia, Perth, WA, Australia.
⁵ School of Pharmacy and Biomedical Sciences, Curtin University, Bentley, WA, Australia.
⁶ Obesity Surgery WA, Murdoch Hospital, Murdoch, WA, Australia.
⁷ Department of Upper GI and Bariatric Surgery, Singapore General Hospital, Singapore, Singapore.
⁸ Department of Anatomy, PathWest Laboratory Medical WA, Pathwest, WA, Australia.
⁹ School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
¹⁰ WA Human Microbiome Collaboration Centre, School of Molecular and Life Sciences, Curtin University, Bentley, WA, Australia.
¹¹ Faculty of Medicine, The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, QLD, Australia.

PMID: 32243703
DOI: 10.1111/liv.14453

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

Leon A Adams et al. Liver Int. 2020 Jun.

. 2020 Jun;40(6):1356-1365.

doi: 10.1111/liv.14453. Epub 2020 Apr 24.

Authors

Affiliations

¹ Medical School, Faculty of Medical and Health Sciences, The University of Western Australia, Perth, WA, Australia.
² Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
³ Storr Liver Centre, The Westmead Institute, University of Sydney, Westmead, NSW, Australia.
⁴ Curtin/UWA Centre for Genetic Origins of Health and Disease, Curtin University and University of Western Australia, Perth, WA, Australia.
⁵ School of Pharmacy and Biomedical Sciences, Curtin University, Bentley, WA, Australia.
⁶ Obesity Surgery WA, Murdoch Hospital, Murdoch, WA, Australia.
⁷ Department of Upper GI and Bariatric Surgery, Singapore General Hospital, Singapore, Singapore.
⁸ Department of Anatomy, PathWest Laboratory Medical WA, Pathwest, WA, Australia.
⁹ School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
¹⁰ WA Human Microbiome Collaboration Centre, School of Molecular and Life Sciences, Curtin University, Bentley, WA, Australia.
¹¹ Faculty of Medicine, The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, QLD, Australia.

PMID: 32243703
DOI: 10.1111/liv.14453

Abstract

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.

Keywords: deoxycholic acid; diet; fibrosis; microbiome; non-alcoholic steatohepatitis.

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References

REFERENCES

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1. Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149:389-397.e10.
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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

Affiliations

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

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

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Substances

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous