Abstract
Alcohol abuse is a significant contributor to the global burden of disease and can lead to tissue damage and organ dysfunction in a subset of alcoholics. However, a subset of alcoholics without any of these predisposing factors can develop alcohol-mediated organ injury. The gastrointestinal tract (GI) could be an important source of inflammation in alcohol-mediated organ damage. The purpose of review was to evaluate mechanisms of alcohol-induced endotoxemia (including dysbiosis and gut leakiness), and highlight the predisposing factors for alcohol-induced dysbiosis and gut leakiness to endotoxins. Barriers, including immunologic, physical, and biochemical can regulate the passage of toxins into the portal and systemic circulation. In addition, a host of environmental interactions including those influenced by circadian rhythms can impact alcohol-induced organ pathology. There appears to be a role for therapeutic measures to mitigate alcohol-induced organ damage by normalizing intestinal dysbiosis and/or improving intestinal barrier integrity. Ultimately, the inflammatory process that drives progression into organ damage from alcohol appears to be multifactorial. Understanding the role of the intestine in the pathogenesis of alcoholic liver disease can pose further avenues for pathogenic and treatment approaches.
Highlights
Alcohol abuse is a significant contributor to the global burden of disease and can lead to tissue damage and organ dysfunction in a subset of alcoholics
Alcohol-induced dysbiosis in rodents can be corrected with beneficial effects on treatment of alcoholic liver disease and by dietary supplementation with either prebiotic oats or probiotic Lactobacillus GG [30,31,46,117,118]
While alcohol is a necessary component in the development of alcoholic liver disease and cirrhosis, only a subset of alcoholics develop cirrhosis and liver failure [20]
Summary
Alcohol abuse is a significant contributor to the global burden of disease and can lead to tissue damage and organ dysfunction in a subset of alcoholics. Approximately 20%–30% of heavy drinkers develop clinically significant alcoholic liver disease (ALD) including alcoholic steatohepatitis and cirrhosis [1] This observation indicates that alcohol consumption is necessary it is not sufficient to cause clinically relevant organ damage [2,3]. Kupffer cells and macrophages within the liver respond to LPS via a myriad of mechanisms including activation of the TLR4 eliciting the production of reactive oxygen species (ROS), leukotrienes, chemokines, as well as cytokines. The production of these factors results in tissue inflammation and contributes to alcohol-induced organ pathology. We will provide an overview of mechanisms of alcohol-induced endotoxemia (i.e., dysbiosis and gut leakiness) and highlight the predisposing factors (e.g., disrupted circadian rhythms) for alcohol-induced dysbiosis and gut leakiness to endotoxins
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