ArticleClinical and molecular hepatology2022
Gut-derived lipopolysaccharide promotes alcoholic hepatosteatosis and subsequent hepatocellular carcinoma by stimulating neutrophil extracellular traps through toll-like receptor 4.
Article in Clinical and molecular hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Neutrophil extracellular traps (NETs) and NETosis in alcohol-associated diseases: A systematic review.Alcohol, clinical & experimental research · 2025Pooled it
- Neutrophil extracellular traps in liver diseases: from molecular mechanisms to therapeutic interventions.Acta pharmacologica Sinica · 2026Review
- Perioperative gut microbial ecology: a new frontier for improving the prognosis of hepatocellular carcinoma surgery.Precision clinical medicine · 2026Review
- The emerging role of neutrophil extracellular traps in liver diseases: a narrative review.Medical molecular morphology · 2026Review
- Persistent NET states link lesion-related microbial signals to the cold tumor-related local restrictive environment: a context-dependent working model.Cell communication and signaling : CCS · 2026Review
- Gut-liver axis molecular mechanisms in alcohol-associated liver disease.Alcohol (Fayetteville, N.Y.) · 2026Review
- The versatile interplay between steatotic liver disease and liver cancer.Nature reviews. Cancer · 2026Review
- Neutrophil extracellular traps: A central player in liver diseases.Hepatology communications · 2026Review
- Decoding the mechanistic basis of liver-muscle communication in health and disease.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Targeting the Toll-Like Receptor 4 Ameliorates Heart Failure in Aged Mice by Inhibiting the Formation of Neutrophil Extracellular Traps.Physiological research · 2026Article
- The Molecular Network of Neutrophil Extracellular Traps in Hepatocellular Carcinoma: Biogenesis, Function, and Therapeutic Implications.Molecules (Basel, Switzerland) · 2026Review
- Microbial Biomarkers for the Prevention and Diagnosis of Alcoholic Liver Disease.Microorganisms · 2026Article
- Alterations in Gut Microbiota and Metabolism in Cirrhotic Portal Hypertension: Implications for Disease Progression.Alimentary pharmacology & therapeutics · 2026Article
- E2F5 Overexpression in Laryngeal Squamous Cell Carcinoma: Associations With Neutrophil Extracellular Traps in the Tumor Microenvironment.World journal of oncology · 2026Article
- The landscape of gut microbiota in hepatocarcinogenesis: a comprehensive review of pathogenesis and therapeutic interventions.International journal of surgery (London, England) · 2026Review
- Gut microbial metabolites in cancer immunomodulation.Molecular cancer · 2025Review
- Microbial Modulation of the Gut-Liver Axis in Autoimmune Liver Diseases.Seminars in liver disease · 2025Review
- Toll Like Receptors Promote High Glucose-Induced Vascular Endothelial Cell Dysfunction by Regulating Neutrophil Extracellular Traps Formation.Inflammation · 2025Article
- Regulatory role of gut microbiota in immunotherapy of hepatocellular carcinoma.Hepatology international · 2025Review
- Roles of the gut microbiota in hepatocellular carcinoma: from the gut dysbiosis to the intratumoral microbiota.Cell death discovery · 2025Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND/
aimsBinge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs).
methodsSerum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used.
resultsA marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated.
conclusionFormation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.
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