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Microbiome and metabolomics in alcoholic liver disease

Raja Ganesan, Ki Tae Sukorcid
Clinical and Molecular Hepatology 2022;28(3):580-582.
Published online: July 1, 2022

Institute for Liver and Digestive Disease, Hallym University, Chuncheon, Korea

Corresponding author : Ki Tae Suk Institute for Liver and Digestive Disease, Hallym University, 1 Hallymdaehak-gil, Chuncheon, 24252, Korea Tel: +82-33-248-3480, Fax: +82-33-248-3481, E-mail: ktsuk@hallym.ac.kr

Editor: Dae Won Jun, Hanyang University College of Medicine, Korea

• Received: June 11, 2022   • Accepted: July 1, 2022

Copyright © 2022 by The Korean Association for the Study of the Liver

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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The gastrointestinal microbiome and metabolomics are the candidate biomarkers for alcoholic liver disease (ALD) [1]. Alcohol-associated liver injury is characterized by oxidative stress, lipid peroxidation, steatosis, iron deposits, hepatocyte damage, and hepatocytes death. These features have been associated with liver inflammation, activation of Kupffer cells and hepatic stellate cells, liver fibrosis, and liver regeneration process. Alcohol use promotes a change in microbiome composition. Microbiota-host co-regulated metabolic pathways are promising targets for clinical needs.
Metabolite profiles such as lipids, fatty acids, carbohydrates, vitamins, proteins, enzymatic compounds, amino acids, and small-molecules profoundly affected host physiology and are being explored for their roles in ALD. The molecular families are shaped by the microbiome with short-chain fatty acids (SCFA; acetate, propionate, and butyrate), aromatic amino acid metabolites, indoles, complex polysaccharides, and host lipids such as sphingolipids and bile acids [2,3]. SCFA were found in human large intestine and involved in microbial fermentation. SCFA play intestinal homeostasis and potent immune regulators. SCFA indicate that gut-brain-liver axis could impaired by alcohol [4,5].
Acetaldehyde is mainly expressed in hepatocytes and acts on hepatic stellate cells (HSCs) in a paracrine manner. Acetaldehyde directly increases expression of collagen-I in HSCs through transcription factors. Acetaldehyde reacts with metabolic components, which help maintain HSC activation. Ethanol increases fatty liver acid synthesis in hepatocytes via sterol regulatory element-binding protein-1c by increasing expression of lipogenic genes [6]. Interleukin (IL)-22 might be used treat to ALD patients because of its antioxidant, anti-apoptotic, anti-steatotic, anti-proliferative, and anti-microbial effects. Corticosteroids increased survival in patients with alcoholic hepatitis.
CXC chemokines such as CXCL12, CXCR4, and vascular endothelial growth factor have increased survival and the degree of hypertension. IL-8 and growth-related oncogene-alpha are parts of CXC chemokines family. These might be industrialized as a therapeutic drug for ALD [7].
Anti-tumor necrosis factor (TNF)-α has an important role in the pathogenies of ALD in animal models. Pentoxifylline blocks transcription of TNF-α which can decrease serum level of TNF-α. S-adenosylmethionine (SAMe) acts as a methyl donor that has protect against ALD through antioxidant functions, and down regulation of TNF-α. SAMe plays as a safe drug for ALD. However, Cochrane report indicated that there have no evidences to support the use of SAMe in ALD patients [8].
The time has come to develop the therapeutic biomarkers via gut-microbiome and metabolome in ALD. Patients with ALD show gut barrier dysfunction. Now, gut-microbiome-centered therapies are novel and associated metabolomics signature that plays a big platform for biomarkers discovery in ALD.
This research was funded by Hallym University Research Fund, and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (NRF-2018M3A9F3020956, NRF-2019R1I1A3A01060447, NRF-2020R1I1A3073530 and NRF2020R1A6A1A03043026).

Authors’ contributions

All authors wrote the manuscript and revised. Ki Tae Suk supervised and approved the manuscript for publication.

Conflicts of Interest

The authors have no conflicts to disclose.

cmh-2022-0171f1.jpg

ALD

alcoholic liver disease

HSC

hepatic stellate cell

IL

interleukin

SAMe

S-adenosylmethionine

SCFA

short-chain fatty acids

TNF

tumor necrosis factor
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Microbiome and metabolomics in alcoholic liver disease
Clin Mol Hepatol. 2022;28(3):580-582.   Published online July 1, 2022
DOI: https://doi.org/10.3350/cmh.2022.0171
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Microbiome and metabolomics in alcoholic liver disease
Clin Mol Hepatol. 2022;28(3):580-582.   Published online July 1, 2022
DOI: https://doi.org/10.3350/cmh.2022.0171
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