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Review
. 2023 Feb 13;24(4):3735.
doi: 10.3390/ijms24043735.

Alcohol, Inflammation, and Microbiota in Alcoholic Liver Disease

Marija Dukić  1 , Tijana Radonjić  1 , Igor Jovanović  1 , Marija Zdravković  1   2 , Zoran Todorović  1   2 , Nemanja Kraišnik  1 , Bojana Aranđelović  1 , Olga Mandić  1 , Višeslav Popadić  1 , Novica Nikolić  1 , Slobodan Klašnja  1 , Andrea Manojlović  1 , Anica Divac  1 , Jasna Gačić  1   2 , Milica Brajković  1 , Svetlana Oprić  1 , Maja Popović  1 , Marija Branković  1   2
Affiliations
Review

Alcohol, Inflammation, and Microbiota in Alcoholic Liver Disease

Marija Dukić et al. Int J Mol Sci. .

Abstract

Alcoholic liver disease (ALD) is a consequence of excessive alcohol use. According to many studies, alcohol represents a significant socioeconomic and health risk factor in today's population. According to data from the World Health Organization, there are about 75 million people who have alcohol disorders, and it is well known that its use leads to serious health problems. ALD is a multimodality spectrum that includes alcoholic fatty liver disease (AFL) and alcoholic steatohepatitis (ASH), consequently leading to liver fibrosis and cirrhosis. In addition, the rapid progression of alcoholic liver disease can lead to alcoholic hepatitis (AH). Alcohol metabolism produces toxic metabolites that lead to tissue and organ damage through an inflammatory cascade that includes numerous cytokines, chemokines, and reactive oxygen species (ROS). In the process of inflammation, mediators are cells of the immune system, but also resident cells of the liver, such as hepatocytes, hepatic stellate cells, and Kupffer cells. These cells are activated by exogenous and endogenous antigens, which are called pathogen and damage-associated molecular patterns (PAMPs, DAMPs). Both are recognized by Toll-like receptors (TLRs), which activation triggers the inflammatory pathways. It has been proven that intestinal dysbiosis and disturbed integrity of the intestinal barrier perform a role in the promotion of inflammatory liver damage. These phenomena are also found in chronic excessive use of alcohol. The intestinal microbiota has an important role in maintaining the homeostasis of the organism, and its role in the treatment of ALD has been widely investigated. Prebiotics, probiotics, postbiotics, and symbiotics represent therapeutic interventions that can have a significant effect on the prevention and treatment of ALD.

Keywords: alcohol; alcoholic hepatitis; inflammation; microbiota.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Modalities of alcoholic liver disease.
Figure 2
Figure 2
Fatty liver biopsy. Hematoxylin and Eosin (H&E) staining. Legend: 1: Lymphocytes; 2: Focal necrosis; 3: Ballooned hepatocytes; 4: Fat accumulation; 5: Kupffer cells.
Figure 3
Figure 3
Metabolism and mechanism of harmful effects of alcohol.
Figure 4
Figure 4
Cells which are involved in pathogenesis of alcoholic liver disease. In the intestinal lumen is the intestinal microbiota, the source of molecules which human organism recognizes as pathogen-associated molecular patterns (PAMPs). The role of lipopolysaccharide (LPS) of Gram-negative bacteria is best studied. It passes through damaged tight junctions (TJ) to the enterohepatic circulation, then to the liver, where it is recognized, among others, by Kupffer cells using Toll-like receptors class 4 (TLRs). In response to this stimulation, Kupffer cells secrete proinflammatory cytokines (IL-6, TNF-α, IL-1β) that lead to hepatocyte damage and the onset or progression of alcoholic liver disease.
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