Clinical and Molecular Hepatology

"Lipopolysaccharide"

Original Article

Gut-derived lipopolysaccharide promotes alcoholic hepatosteatosis and subsequent hepatocellular carcinoma by stimulating neutrophil extracellular traps through toll-like receptor 4: Yang Liu, Xin Zhang, Shuo Chen, Jiazhong Wang, Shuo Yu, Yiming Li, Meng Xu, Harouna Aboubacar, Junhui Li, Tao Shan, Jixin Wang, Gang Cao; Clin Mol Hepatol 2022;28(3):522-539.
Published online May 4, 2022; DOI: https://doi.org/10.3350/cmh.2022.0039

Background/Aims
Binge 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).
Methods
Serum 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.
Result
s: A 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.
Conclusions
Formation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.

Citations

Citations to this article as recorded by

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Qun Zhang, Jinghua Cui, Yixin Hou, Lining Guo, Hai Li, Guiqin Zhou, Xiaojing Wang, Bingbing Zhu, Ke Shi, Yi Zhang, Yufei Bi, Yanqiu Li, Lina Sun, Ying Feng, Jing Yuan, Xianbo Wang
Alimentary Pharmacology & Therapeutics.2026; 63(4): 538. CrossRef
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Gursimran Singh, Shazia Ansari, Satyam Yadav, Khadga Raj Aran
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Frontiers in Immunology.2026;[Epub] CrossRef
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Zhi-Bo Yan, Cheng-Long Han, Ji-Sen Jia, Han Li, Dong-Hai Lu, Qi-Hang Cao, Yu-Xuan Wang, Ke-Fan Jiao, Qiao He, Sheng-Xuan Peng, Dao-Lin Zhang, Qiang Wang, Tao Li
International Journal of Surgery.2026; 112(1): 1673. CrossRef
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Ki M. Mak, Aditya C. Shekhar
The Anatomical Record.2025; 308(3): 975. CrossRef
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Kin Lam Yu, Sj Shen
European Journal of Cancer.2025; 216: 115195. CrossRef
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Lexin Fang, Yu Song, Jiangtao Chen, Yueping Ding
Frontiers in Immunology.2025;[Epub] CrossRef
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Food & Function.2025; 16(13): 5393. CrossRef
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Food Science and Human Wellness.2025; 14(6): 9250146. CrossRef
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Food Research International.2025; 222: 117639. CrossRef
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Jie Mao, Shuang Wu, Zelin Yan, Guiping Huang, Yihua Yu
Frontiers in Immunology.2025;[Epub] CrossRef
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Molecular Cancer.2025;[Epub] CrossRef
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Peiliang Shen, Peng Cheng, Yanan Li, Gangfan Zong, Rui Deng, Cheng Qian, Yang Zhao, Zhonghong Wei, Yin Lu
European Journal of Pharmacology.2024; 962: 176217. CrossRef
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International Journal of Molecular Sciences.2024; 25(3): 1381. CrossRef
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Trends in Endocrinology & Metabolism.2024; 35(11): 1006. CrossRef
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International Immunopharmacology.2024; 141: 112923. CrossRef
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American Journal of Clinical and Experimental Immunology.2024; 13(5): 233. CrossRef
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Frontiers in Pharmacology.2024;[Epub] CrossRef
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Journal of Hepatology.2023; 79(1): e29. CrossRef
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Carbohydrate Polymers.2023; 303: 120453. CrossRef
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Frontiers in Immunology.2023;[Epub] CrossRef
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Journal of Experimental & Clinical Cancer Research.2023;[Epub] CrossRef
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Editorial

Liver fibrosis, cirrhosis, and portal hypertension

Leaky gut-derived tumor necrosis factor-α causes sarcopenia in patients with liver cirrhosis: Takumi Kawaguchi, Takuji Torimura; Clin Mol Hepatol 2022;28(2):177-180.
Published online August 26, 2021; DOI: https://doi.org/10.3350/cmh.2021.0246

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Cells.2025; 14(6): 428. CrossRef
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S. N. Mekhtiyev, O. A. Mekhtiyeva, O. M. Berko, A. M. Kolodkin
Experimental and Clinical Gastroenterology.2023; (12): 130. CrossRef

9,195 View
197 Download
6 Web of Science
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Review

Liver fibrosis, cirrhosis, and portal hypertension

The role of gut-liver axis in the pathogenesis of liver cirrhosis and portal hypertension: Yeon Seok Seo, Vijay H. Shah; Korean J Hepatol 2012;18(4):337-346.
Published online December 21, 2012; DOI: https://doi.org/10.3350/cmh.2012.18.4.337

Abstract
PDF

Because of the anatomical position and its unique vascular system, the liver is susceptible to the exposure to the microbial products from the gut. Although large amount of microbes colonize in the gut, translocation of the microbes or microbial products into the liver and systemic circulation is prevented by gut epithelial barrier function and cleansing and detoxifying functions of the liver in healthy subjects. However, when the intestinal barrier function is disrupted, large amount of bacterial products can enter into the liver and systemic circulation and induce inflammation through their receptors. Nowadays, there have been various reports suggesting the role of gut flora and bacterial translocation in the pathogenesis of chronic liver disease and portal hypertension. This review summarizes the current knowledge about bacterial translocation and its contribution to the pathogenesis of chronic liver diseases and portal hypertension.

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Journal of the Formosan Medical Association.2022;[Epub] CrossRef
Alterations in circadian rhythms aggravate Acetaminophen-induced liver injury in mice by influencing Acetaminophen metabolization and increasing intestinal permeability
Kun Zhang, Xiude Fan, Xiaoyun Wang, Xiaoge Zhang, Lu Zeng, Na Li, Qunying Han, Yi Lv, Zhengwen Liu
Bioengineered.2022; 13(5): 13118. CrossRef
7-O-(2- (Propylamino)-2-oxoethyl) hesperetin attenuates inflammation and protects against alcoholic liver injury by NLRP12
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Food & Function.2022; 13(10): 5626. CrossRef
Inchinkoto, the Traditional Japanese Kampo Medicine, Enhances Intestinal Epithelial Barrier Function In Vitro
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Evidence-Based Complementary and Alternative Medicine.2022; 2022: 1. CrossRef
New perspective on fecal microbiota transplantation in liver diseases
Ki Tae Suk, Hong Koh
Journal of Gastroenterology and Hepatology.2022; 37(1): 24. CrossRef
Influence of Gut–Liver Axis on Portal Hypertension in Advanced Chronic Liver Disease: The Gut Microbiome as a New Protagonist in Therapeutic Management
Francesco Santopaolo, Gaetano Coppola, Lucia Giuli, Antonio Gasbarrini, Francesca Romana Ponziani
Microbiology Research.2022; 13(3): 539. CrossRef
Food-Specific IgE and IgG Antibodies in Patients With Chronic Rhinosinusitis With Nasal Polyps: A Case–Control Study
Rafaela Veloso-Teles, Rui Cerejeira, Débora Rodrigues, Rosa Roque-Farinha, Christian von Buchwald
Ear, Nose & Throat Journal.2021; 100(3): 177. CrossRef
Interplay of cardiovascular mediators, oxidative stress and inflammation in liver disease and its complications
Csaba Matyas, György Haskó, Lucas Liaudet, Eszter Trojnar, Pal Pacher
Nature Reviews Cardiology.2021; 18(2): 117. CrossRef
TNFR1 and the TNFα axis as a targetable mediator of liver injury from stereotactic body radiation therapy
Matthew M. Cousins, Emily Morris, Christopher Maurino, Theresa P. Devasia, David Karnak, Dipankar Ray, Neehar D. Parikh, Dawn Owen, Randall K. Ten Haken, Matthew J. Schipper, Theodore S. Lawrence, Kyle C. Cuneo
Translational Oncology.2021; 14(1): 100950. CrossRef
The Role of Intestinal Bacteria and Gut–Brain Axis in Hepatic Encephalopathy
Zefeng Chen, Jingsheng Ruan, Dinghua Li, Min Wang, Zhiwei Han, Wenxia Qiu, Guobin Wu
Frontiers in Cellular and Infection Microbiology.2021;[Epub] CrossRef
The Role of Microbiota in Primary Sclerosing Cholangitis and Related Biliary Malignancies
Burcin Özdirik, Tobias Müller, Alexander Wree, Frank Tacke, Michael Sigal
International Journal of Molecular Sciences.2021; 22(13): 6975. CrossRef
Intestinal Permeability Is a Mechanical Rheostat in the Pathogenesis of Liver Cirrhosis
Norihisa Nishimura, Kosuke Kaji, Koh Kitagawa, Yasuhiko Sawada, Masanori Furukawa, Takahiro Ozutsumi, Yukihisa Fujinaga, Yuki Tsuji, Hiroaki Takaya, Hideto Kawaratani, Kei Moriya, Tadashi Namisaki, Takemi Akahane, Hiroshi Fukui, Hitoshi Yoshiji
International Journal of Molecular Sciences.2021; 22(13): 6921. CrossRef
Intestinal Barrier in Human Health and Disease
Natalia Di Tommaso, Antonio Gasbarrini, Francesca Romana Ponziani
International Journal of Environmental Research and Public Health.2021; 18(23): 12836. CrossRef
Friend or Foe? Impacts of Dietary Xylans, Xylooligosaccharides, and Xylanases on Intestinal Health and Growth Performance of Monogastric Animals
Jonathan T. Baker, Marcos E. Duarte, Debora M. Holanda, Sung Woo Kim
Animals.2021; 11(3): 609. CrossRef
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Clinical and Molecular Hepatology.2021; 27(3): 425. CrossRef
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Hepatology.2021; 74(1): 72. CrossRef
Leaky Gut and Gut-Liver Axis in Liver Cirrhosis: Clinical Studies Update
Hiroshi Fukui
Gut and Liver.2021; 15(5): 666. CrossRef
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Expert Opinion on Investigational Drugs.2021; 30(9): 985. CrossRef
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Yang Wang, Yifan Zhang, Yun Liu, Jun Xu, Yulan Liu
Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef
Significance of gut microbiota in alcoholic and non-alcoholic fatty liver diseases
Satya Priya Sharma, Ki Tae Suk, Dong Joon Kim
World Journal of Gastroenterology.2021; 27(37): 6161. CrossRef
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Yu-Xia Lu, Yi-Zhong Chang, Ping Liang, Chang-Qing Yang
Infectious Diseases and Therapy.2021; 10(3): 1519. CrossRef
PTP1B promotes macrophage activation by regulating the NF-κB pathway in alcoholic liver injury
Lei Yang, Ying-yin Sun, Ya-ru Liu, Na-na Yin, Fang-tian Bu, Hai-xia Yu, Xiao-sa Du, Jun Li, Cheng Huang
Toxicology Letters.2020; 319: 11. CrossRef
The assembly of integrated rat intestinal‐hepatocyte cultures
Anjaney Kothari, Padmavathy Rajagopalan
Bioengineering & Translational Medicine.2020;[Epub] CrossRef
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Vanessa Weir, K. Rajender Reddy
Clinics in Liver Disease.2020; 24(2): 243. CrossRef
The correlation between intestinal mucosal lesions and hepatic dysfunction in patients without chronic liver disease
Li-Hao Wu, Mei-Hui Chen, Jie-Yi Cai, Yu Yuan, Li-Quan Wu, Hui-Min Zhou, Lan Li, Kayiu Wan, Xing-Xiang He
Medicine.2020; 99(7): e18837. CrossRef
Maternal hepatitis B or hepatitis C virus carrier status and long‐term infectious morbidity of the offspring: A population‐based cohort study
Naim Abu Freha, Tamar Wainstock, Liat Poupko, Avni Yonat Shemer, Ruslan Sergienko, Eyal Sheiner
Journal of Viral Hepatitis.2020; 27(8): 794. CrossRef
The role of oligosaccharides and polysaccharides of xylan and mannan in gut health of monogastric animals
Utsav P. Tiwari, Stephen A. Fleming, Muhammed S. Abdul Rasheed, R. Jha, Ryan N. Dilger
Journal of Nutritional Science.2020;[Epub] CrossRef
Nonalcoholic fatty liver disease and portal hypertension
Marvin Ryou, Nicholas Stylopoulos, Gyorgy Baffy
Exploration of Medicine.2020; 1(3): 149. CrossRef
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Anna Zagórska, Paqui G Través, Lidia Jiménez-García, Jenna D Strickland, Joanne Oh, Francisco J Tapia, Rafael Mayoral, Patrick Burrola, Bryan L Copple, Greg Lemke
Life Science Alliance.2020; 3(8): e202000694. CrossRef
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Yong-Tao Li, Jian-Rong Huang, Mei-Lian Peng
BioMed Research International.2020; 2020: 1. CrossRef
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Daniel Osei-Bordom, Amber G. Bozward, Ye Htun Oo
Cellular Immunology.2020; 357: 104195. CrossRef
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Joong-won Jeon, Nakwon Choi, Seung Hwan Lee, Jong Hwan Sung
Biomedical Microdevices.2020;[Epub] CrossRef
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Gut Microbes.2020; 12(1): 1838236. CrossRef
Determinación de la microbiota intestinal en pacientes cirróticos de población mestizo-mexicana
C. Pérez-Monter, I. Escalona-Nandez, A. Estanes-Hernández, L.G. Noriega-López, A. Torre-Delgadillo
Revista de Gastroenterología de México.2019; 84(1): 26. CrossRef
Intestinal microbiota assessment in cirrhotic patients from a Mexican mestizo population
C. Pérez-Monter, I. Escalona-Nandez, A. Estanes-Hernández, L.G. Noriega-López, A. Torre-Delgadillo
Revista de Gastroenterología de México (English Edition).2019; 84(1): 26. CrossRef
Circulating markers of gut barrier function associated with disease severity in primary sclerosing cholangitis
Amandeep K. Dhillon, Martin Kummen, Marius Trøseid, Sissel Åkra, Evaggelia Liaskou, Bjørn Moum, Mette Vesterhus, Tom H. Karlsen, Ingebjørg Seljeflot, Johannes R. Hov, Gabriele Missale
Liver International.2019; 39(2): 371. CrossRef
Plasma levels of soluble ST2, but not IL-33, correlate with the severity of alcoholic liver disease
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Journal of Cellular and Molecular Medicine.2019; 23(2): 887. CrossRef
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Hepatology Communications.2019; 3(4): 456. CrossRef
Mechanism of neoagarotetraose protects against intense exercise-induced liver injury based on molecular ecological network analysis
Xin Chen, Jiahong Yu, Changhu Xue, Yuming Wang, Qingjuan Tang, Xiangzhao Mao
Bioscience, Biotechnology, and Biochemistry.2019; 83(7): 1227. CrossRef
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Yang Wang, Yanping Wu, Baikui Wang, Han Xu, Xiaoqiang Mei, Xiaogang Xu, Xiaoping Zhang, Jiajia Ni, Weifen Li
Frontiers in Microbiology.2019;[Epub] CrossRef
Role of Gut Dysbiosis in Liver Diseases: What Have We Learned So Far?
Hiroshi Fukui
Diseases.2019; 7(4): 58. CrossRef
Non-viral liver diseases: pathogenetic approaches to therapy
M. A. Osadchuk, E. D. Mironova
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Original Article

An Experimental Model of Hepatic Fibrosis Induced by Alcohol and CCl₄ : Can the Lipopolysaccharide Prevent Liver Injury Induced by Alcohol and CCl₄ ?: Hee Bok Chae, M.D., Lee Chan Jang, M.D.*, Seon Mee Park, M.D., Bo Ra Son, M.D.†, Rohyun Sung, M.D.‡, Jae Woon Choi, M.D.*; Korean J Hepatol 2002;8(2):173-178.

Abstract
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Background/Aims
It is well known that alcohol enhances the toxicity of CCL₄. We tried to establish an alcoholic liver cirrhosis model by administration of alcohol and CCL₄ to rats. We also wanted to know the hepatoprotective effect of low doses of lipopolysaccharide(LPS) in this animal model. Methods: Of 20 female adult rats, 8 were ingested with alcohol ad libitum(group 1) Another 6 were ingested with 10% alcohol and 50% 1mL/kg CCL₄ intragastrically by Sonde twice a week(group 2) The remaining 6 were ingested with 10% alcohol, CCL₄, and 0.1mg/kg LPS intraperitoneally twice a week(group 3) The fibrosis was evaluated semiquantitatively on a scale of 0(none) to 3(cirrhosis). Results: 1) After 10 weks, septal fibrosis or cirrhosis was produced in 9 out of 12 rats in groups 2 and 3 but there was no fibrotic change in group 1. 2) There was no significant difference in pathological grading between groups 2 and 3. Conclusions: Hepatic fibrosis or cirrhosis can be sufficiently induced by alcohol and repetitive CCL₄ ingestion for 10 weeks. We can not prove the hepatoprotective effect of low dose LPS by semiquantitative evaluation of pathological grading.(Korean J Hepatol 2002;8:173-178)