Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Feb 23;10(3):524.
doi: 10.3390/biomedicines10030524.

The Role of Gut-Liver Axis in Gut Microbiome Dysbiosis Associated NAFLD and NAFLD-HCC

Qian Song  1   2 , Xiang Zhang  1   2
Affiliations
Review

The Role of Gut-Liver Axis in Gut Microbiome Dysbiosis Associated NAFLD and NAFLD-HCC

Qian Song et al. Biomedicines. .

Abstract

Nonalcoholic fatty liver disease (NAFLD) is considered as one of the most prevalent chronic liver diseases worldwide due to the rapidly rising prevalence of obesity and metabolic syndrome. As a hepatic manifestation of metabolic disease, NAFLD begins with hepatic fat accumulation and progresses to hepatic inflammation, termed as non-alcoholic steatohepatitis (NASH), hepatic fibrosis/cirrhosis, and finally leading to NAFLD-related hepatocellular carcinoma (NAFLD-HCC). Accumulating evidence showed that the gut microbiome plays a vital role in the initiation and progression of NAFLD through the gut-liver axis. The gut-liver axis is the mutual communication between gut and liver comprising the portal circulation, bile duct, and systematic circulation. The gut microbiome dysbiosis contributes to NAFLD development by dysregulating the gut-liver axis, leading to increased intestinal permeability and unrestrained transfer of microbial metabolites into the liver. In this review, we systematically summarized the up-to-date information of gut microbiome dysbiosis and metabolomic changes along the stages of steatosis, NASH, fibrosis, and NAFLD-HCC. The components and functions of the gut-liver axis and its association with NAFLD were then discussed. In addition, we highlighted current knowledge of gut microbiome-based treatment strategies targeting the gut-liver axis for preventing NAFLD and its associated HCC.

Keywords: gut microbiome; gut–liver axis; intestinal barrier; metabolites; non-alcoholic fatty liver disease.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The diagrammatic representation of gut–liver axis. The communication between gut and liver in NAFLD is the intestinal barrier, which is composed of mucus layer, intestinal epithelium, mucosal immune system, and gut vascular barrier (GVB). The gut microbiota and their metabolites as well as some proinflammatory products can pass through the intestinal barrier and enter the liver through the portal system. In the liver, they can promote or inhibit the progression of NAFLD through different mechanisms. Meanwhile, liver can also regulate intestinal function and gut microbiota balance through the bile acid circulation, which is an important enterohepatic circulation in regulating NAFLD (Created with BioRender.com).
Figure 2
Figure 2
The role of gut–liver axis in the gut microbiota dysbiosis and microbiome-based NAFLD treatment. When the gut microbiota is in homeostasis, it is difficult for the pathogenic bacteria and metabolites to go through the intestinal barrier and reach the liver. When the gut microbiota is dysbiosis, the intestinal barrier is damaged (decreased mucus layer, increased epithelium, and endothelium layer permeability); thus, the pathogenic bacteria and metabolites can easily go through the intestinal barrier, come to the portal system, and finally reach the liver, where they can promote NAFLD progression. Microbiome-based treatment (probiotics and beneficial metabolites) can repair the intestinal barrier and the beneficial metabolites can reach the liver through the portal vein to prevent NAFLD progression (Created with BioRender.com, https://biorender.com/, accessed on 4 February 2022).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Blond E., Disse E., Cuerq C., Drai J., Valette P.-J., Laville M., Thivolet C., Simon C., Caussy C. EASL–EASD–EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease in severely obese people: Do they lead to over-referral? Diabetologia. 2017;60:1218–1222. doi: 10.1007/s00125-017-4264-9. - DOI - PubMed
    1. Powell E.E., Wong V.W.-S., Rinella M. Non-alcoholic fatty liver disease. Lancet. 2021;397:2212–2224. doi: 10.1016/S0140-6736(20)32511-3. - DOI - PubMed
    1. Ge X., Zheng L., Wang M., Du Y., Jiang J. Prevalence trends in non-alcoholic fatty liver disease at the global, regional and national levels, 1990–2017: A population-based observational study. BMJ Open. 2020;10:e036663. doi: 10.1136/bmjopen-2019-036663. - DOI - PMC - PubMed
    1. Fazel Y., Koenig A.B., Sayiner M., Goodman Z.D., Younossi Z.M. Epidemiology and natural history of non-alcoholic fatty liver disease. Metabolism. 2016;65:1017–1025. doi: 10.1016/j.metabol.2016.01.012. - DOI - PubMed
    1. Cariou B., Byrne C.D., Loomba R., Sanyal A.J. Nonalcoholic fatty liver disease as a metabolic disease in humans: A literature review. Diabetes Obes. Metab. 2021;23:1069–1083. doi: 10.1111/dom.14322. - DOI - PMC - PubMed