Alcohol abuse has become a serious problem across the globe, affecting millions of lives. It is one of the main causative agents for a variety of serious illnesses, including all liver diseases. Alcoholic liver disease (ALD) is caused by chronic alcohol consumption and is the major reason for increasing mortality rates worldwide, making up 4% of the global burden of disease. The liver is considered the major site for alcohol metabolism.

Alcohol dehydrogenase, which is present in the liver, catalyses the oxidation of ethanol, as does, to a lesser extent, the cytochrome P450 dependent oxidizing system (CYP2E1). Due to ethanol metabolism by CYP2E1 and NADH oxidation, the production of reactive oxygen species (ROS) occurs, causing lipid peroxidation. This results in the formation of metabolites such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE). Both MDA and HNE form adducts with proteins and induce oxidative stress and inflammation in hepatocytes. All these processes lead to further liver tissue damage and enhance the progression of ALD. In recent years, the gut microbiome has become the focus of extensive research and has become considered almost a second brain. Gut microbiota consists of the complex microbial population present in the gastrointestinal tract (GI tract) of the human body. Any disturbance in microbial composition leads to the disruption of the symbiosis of microbes and host, causing dysbiosis, and alcohol consumption is one of the major reasons for gut dysbiosis. It causes alterations in the composition of mucosa-associated colonic bacteria, and this disturbed microbial composition of the gut causes increased gut permeability by disrupting tight junctions. This leads to the entry of gram-negative bacteria and other endotoxins, such as lipopolysaccharides (LPS), into the portal vein circulation and finally to the liver. TLR-4, along with its co-receptor CD14, binds to LPSs in the presence of lipopolysaccharide-binding protein (LBP), resulting in the increased LPS concentration in portal circulation. This in turn results in the activation of Kupffer cells, which then causes the induction of pro-inflammatory cytokines and chemokines. Despite extensive research exploring the pathophysiology of ALD, no targeted therapies or approved drugs are yet available. Hence, the quest to find a safe therapeutic regime is increasingly significant.

The aim of this Special Issue is to explore the role of gut microbiota in therapeutic approaches for alcoholic liver disease. With the explored symbiotic relation between gut microbiota and the liver, the use of probiotics has successfully been proven beneficial in reversing gut dysbiosis and maintaining liver homeostasis in ALD. We welcome both original research and review articles.

Potential topics include but are not limited to the following:

• Interactions between nutrients, gut microbiota, and host metabolism
• Identifying the novel molecular mechanisms involved in the crosstalk between inflammation and gut health
• Alcohol and its role in gut dysbiosis
• Alcohol, oxidative stress, liver fibrosis, and its modulation by probiotics
• Characterization of novel therapeutic molecules from probiotics in the prevention of alcoholic liver disease
• Role of DNA and acetaldehyde adducts in hepatic cell death
• Alcohol, oxidative stress, and ER stress crosstalk in alcoholic liver disease
• Role of gut microbiota in macrophage polarization
• Role of macrophages in the progression of alcoholic liver disease
• Possible therapeutic interventions for treating host metabolism dysfunction