The Intestinal Microbiota in the Development of Chronic Liver Disease: Current Status

Overview

Journal Diagnostics (Basel)

Specialty Radiology

Date 2023 Sep 28

PMID 37761327

Authors

Josip Stojic

Michal Kukla

Ivica Grgurevic

Affiliations

Soon will be listed here.

Abstract

Chronic liver disease (CLD) is a significant global health burden, leading to millions of deaths annually. The gut-liver axis plays a pivotal role in this context, allowing the transport of gut-derived products directly to the liver, as well as biological compounds from the liver to the intestine. The gut microbiota plays a significant role in maintaining the health of the digestive system. A change in gut microbiome composition as seen in dysbiosis is associated with immune dysregulation, altered energy and gut hormone regulation, and increased intestinal permeability, contributing to inflammatory mechanisms and damage to the liver, irrespective of the underlying etiology of CLD. The aim of this review is to present the current knowledge about the composition of the intestinal microbiome in healthy individuals and those with CLD, including the factors that affect this composition, the impact of the altered microbiome on the liver, and the mechanisms by which it occurs. Furthermore, this review analyzes the effects of gut microbiome modulation on the course of CLD, by using pharmacotherapy, nutrition, fecal microbiota transplantation, supplements, and probiotics. This review opens avenues for the translation of knowledge about gut-liver interplay into clinical practice as an additional tool to fight CLD and its complications.

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References

Ruhlemann M, Liwinski T, Heinsen F, Bang C, Zenouzi R, Kummen M . Consistent alterations in faecal microbiomes of patients with primary sclerosing cholangitis independent of associated colitis. Aliment Pharmacol Ther. 2019; 50(5):580-589. PMC: 6899739. DOI: 10.1111/apt.15375. View

Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J . Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013; 144(7):1426-37, 1437.e1-9. DOI: 10.1053/j.gastro.2013.02.042. View

Albillos A, de la Hera A, Gonzalez M, Moya J, Calleja J, Monserrat J . Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement. Hepatology. 2002; 37(1):208-17. DOI: 10.1053/jhep.2003.50038. View

Riva A, Borgo F, Lassandro C, Verduci E, Morace G, Borghi E . Pediatric obesity is associated with an altered gut microbiota and discordant shifts in Firmicutes populations. Environ Microbiol. 2016; 19(1):95-105. PMC: 5516186. DOI: 10.1111/1462-2920.13463. View

Huang Y, Fan X, Wang Z, Zhou J, Tian X, Li N . Identification of helicobacter species in human liver samples from patients with primary hepatocellular carcinoma. J Clin Pathol. 2004; 57(12):1273-7. PMC: 1770525. DOI: 10.1136/jcp.2004.018556. View

Lu H, Wu Z, Xu W, Yang J, Chen Y, Li L . Intestinal microbiota was assessed in cirrhotic patients with hepatitis B virus infection. Intestinal microbiota of HBV cirrhotic patients. Microb Ecol. 2011; 61(3):693-703. DOI: 10.1007/s00248-010-9801-8. View

Loomba R, Seguritan V, Li W, Long T, Klitgord N, Bhatt A . Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease. Cell Metab. 2017; 25(5):1054-1062.e5. PMC: 5502730. DOI: 10.1016/j.cmet.2017.04.001. View

Haziot A, Chen S, Ferrero E, Low M, Silber R, Goyert S . The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage. J Immunol. 1988; 141(2):547-52. View

Mencin A, Kluwe J, Schwabe R . Toll-like receptors as targets in chronic liver diseases. Gut. 2009; 58(5):704-20. PMC: 2791673. DOI: 10.1136/gut.2008.156307. View

10.

Fukui H . Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia. World J Hepatol. 2015; 7(3):425-42. PMC: 4381167. DOI: 10.4254/wjh.v7.i3.425. View

11.

Mookerjee R, Pavesi M, Thomsen K, Mehta G, Macnaughtan J, Bendtsen F . Treatment with non-selective beta blockers is associated with reduced severity of systemic inflammation and improved survival of patients with acute-on-chronic liver failure. J Hepatol. 2015; 64(3):574-82. DOI: 10.1016/j.jhep.2015.10.018. View

12.

Ishimoto T, Lanaspa M, Rivard C, Roncal-Jimenez C, Orlicky D, Cicerchi C . High-fat and high-sucrose (western) diet induces steatohepatitis that is dependent on fructokinase. Hepatology. 2013; 58(5):1632-43. PMC: 3894259. DOI: 10.1002/hep.26594. View

13.

Tsai C, Chen M, Wang Y, Chu C, Huang Y, Lin H . Proton Pump Inhibitors Increase Risk for Hepatic Encephalopathy in Patients With Cirrhosis in A Population Study. Gastroenterology. 2016; 152(1):134-141. DOI: 10.1053/j.gastro.2016.09.007. View

14.

Weiss D . The great escape: microbiotal LPS takes a toll on the liver. Cancer Prev Res (Phila). 2012; 5(9):1078-80. PMC: 3439157. DOI: 10.1158/1940-6207.CAPR-12-0248. View

15.

Grander C, Adolph T, Wieser V, Lowe P, Wrzosek L, Gyongyosi B . Recovery of ethanol-induced depletion ameliorates alcoholic liver disease. Gut. 2017; 67(5):891-901. DOI: 10.1136/gutjnl-2016-313432. View

16.

Keshavarzian A, Choudhary S, Holmes E, Yong S, Banan A, Jakate S . Preventing gut leakiness by oats supplementation ameliorates alcohol-induced liver damage in rats. J Pharmacol Exp Ther. 2001; 299(2):442-8. View

17.

Pezzino S, Sofia M, Faletra G, Mazzone C, Litrico G, La Greca G . Gut-Liver Axis and Non-Alcoholic Fatty Liver Disease: A Vicious Circle of Dysfunctions Orchestrated by the Gut Microbiome. Biology (Basel). 2022; 11(11). PMC: 9687983. DOI: 10.3390/biology11111622. View

18.

Inagaki T, Moschetta A, Lee Y, Peng L, Zhao G, Downes M . Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc Natl Acad Sci U S A. 2006; 103(10):3920-5. PMC: 1450165. DOI: 10.1073/pnas.0509592103. View

19.

Keshavarzian A, Farhadi A, Forsyth C, Rangan J, Jakate S, Shaikh M . Evidence that chronic alcohol exposure promotes intestinal oxidative stress, intestinal hyperpermeability and endotoxemia prior to development of alcoholic steatohepatitis in rats. J Hepatol. 2009; 50(3):538-47. PMC: 2680133. DOI: 10.1016/j.jhep.2008.10.028. View

20.

Rao R . Endotoxemia and gut barrier dysfunction in alcoholic liver disease. Hepatology. 2009; 50(2):638-44. PMC: 6209509. DOI: 10.1002/hep.23009. View