Key Signaling in Alcohol-Associated Liver Disease: The Role of Bile Acids

Abstract

Alcohol-associated liver disease (ALD) is a spectrum of diseases, the onset and progression of which are due to chronic alcohol use. ALD ranges, by increasing severity, from hepatic steatosis to alcoholic hepatitis (AH) and alcohol-associated cirrhosis (AC), and in some cases, can lead to the development of hepatocellular carcinoma (HCC). ALD continues to be a significant health burden and is now the main cause of liver transplantations in the United States. ALD leads to biological, microbial, physical, metabolic, and inflammatory changes in patients that vary depending on disease severity. ALD deaths have been increasing in recent years and are projected to continue to increase. Current treatment centers focus on abstinence and symptom management, with little in the way of resolving disease progression. Due to the metabolic disruption and gut dysbiosis in ALD, bile acid (BA) signaling and metabolism are also notably affected and play a prominent role in disease progression in ALD, as well as other liver disease states, such as non-alcoholic fatty liver disease (NAFLD). In this review, we summarize the recent advances in the understanding of the mechanisms by which alcohol consumption induces hepatic injury and the role of BA-mediated signaling in the pathogenesis of ALD.

Salmon sperm DNA prevents acute liver injury by regulating alcohol‐induced steatosis and restores chronic hepatosis via alleviating inflammation and apoptosis

“…Bile acids are synthesized by the liver and can be excreted from the liver. When liver cells are damaged, the uptake of bile acids is blocked, leading to an increase in the level of bile acids in the blood, therefore, the measurement of bile acids in the serum is also an important indicator for evaluating liver damage (Manley & Ding, 2015; Way et al, 2022). Figure 8 shows that serum bile acid levels in mice were significantly elevated after long‐term alcohol intake, indicating that alcohol causes impaired bile acid uptake and severe hepatocyte damage.…”

Alcohol-dependent downregulation of apolipoprotein H exacerbates fatty liver and gut microbiota dysbiosis in mice

“…Alcohol-related liver disease is widely believed to be related to human alcohol metabolism, gender, genetic and environmental factors, diet, and microbiome. However, the metabolic disruption and gut dysbiosis, especially affecting bile acid signaling and metabolism, play a prominent role in disease progression in ALD [ 5 ]. The present study was investigated the effects of ApoH on chronic and binge ethanol-induced liver injury and gut microbiota dysbiosis.…”

“…The pathogenic factors of ALD are associated with alcohol metabolism, gender, genetic and environmental factors, diet, and the microbiome. Metabolic disruption and gut dysbiosis are the major pathophysiologic mechanisms of ALD and play a prominent function in the progression of alcohol associated liver injury [3][4][5][6]. Therefore, there is an urgent need to identify clinical unmet needs in ALD and clarify the precise mechanism underlying ALD pathogenesis.…”

Protective Effect of Polyphenols, Protein, Peptides, and Polysaccharides on Alcoholic Liver Disease: A Review of Research Status and Molecular Mechanisms

“…A healthy diet is an important factor in maintaining the balance of gut microbiota and bile acid homeostasis. However, alcohol exposure alters multiple metabolic pathways, including bile acid metabolism and cholesterol metabolism, and leads to inflammatory responses and organ damage . The possible mechanisms of bile acid-induced liver injury are the changes of gut microbiota induced by alcohol exposure and the increased production of secondary bile acids in the small intestine, which increase the intestinal reabsorption of bile acids back to the liver and stimulate the activation of NF-κB.…”