Journal
JOURNAL OF GASTROINTESTINAL SURGERY
Volume 26, Issue 3, Pages 671-683Publisher
SPRINGER
DOI: 10.1007/s11605-021-05188-7
Keywords
NAFLD; ALD; LPS; Gut barrier; Microbiome
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Hepatosteatosis is the earliest stage in the pathogenesis of nonalcoholic fatty liver disease and alcoholic liver disease, strongly linked with obesity. Gut dysbiosis and gut barrier dysfunction crucially contribute to the development of chronic liver disease. Treatments targeting the gut microbiome and gut barrier have shown potential benefits in attenuating liver inflammation.
Background Hepatosteatosis is the earliest stage in the pathogenesis of nonalcoholic fatty (NAFLD) and alcoholic liver disease (ALD). As NAFLD is affecting 10-24% of the general population and approximately 70% of obese patients, it carries a large economic burden and is becoming a major reason for liver transplantation worldwide. ALD is a major cause of morbidity and mortality causing 50% of liver cirrhosis and 10% of liver cancer related death. Increasing evidence has accumulated that gut-derived factors play a crucial role in the development and progression of chronic liver diseases. Methods A selective literature search was conducted in Medline and PubMed, using the terms nonalcoholic fatty liver disease, alcoholic liver disease, lipopolysaccharide, gut barrier, and microbiome. Results Gut dysbiosis and gut barrier dysfunction both contribute to chronic liver disease by abnormal regulation of the gut-liver axis. Thereby, gut-derived lipopolysaccharides (LPS) are a key factor in inducing the inflammatory response of liver tissue. The review further underlines that endotoxemia is observed in both NAFLD and ALD patients. LPS plays an important role in conducting liver damage through the LPS-TLR4 signaling pathway. Treatments targeting the gut microbiome and the gut barrier such as fecal microbiota transplantation (FMT), probiotics, prebiotics, synbiotics, and intestinal alkaline phosphatase (IAP) represent potential treatment modalities for NAFLD and ALD. Conclusions The gut-liver axis plays an important role in the development of liver disease. Treatments targeting the gut microbiome and the gut barrier have shown beneficial effects in attenuating liver inflammation and need to be further investigated.
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