Review
Biochemistry & Molecular Biology
Francesca Fianchi, Antonio Liguori, Antonio Gasbarrini, Antonio Grieco, Luca Miele
Summary: NAFLD, the leading cause of liver disease worldwide, requires efforts in identifying pathogenetic factors and new therapeutic approaches. The gut-liver axis plays a key role in the pathogenesis of NAFLD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Sonja Lang, Anna Martin, Xinlian Zhang, Fedja Farowski, Hilmar Wisplinghoff, Maria J. G. T. Vehreschild, Marcin Krawczyk, Angela Nowag, Anne Kretzschmar, Claus Scholz, Philipp Kasper, Christoph Roderburg, Raphael Mohr, Frank Lammert, Frank Tacke, Bernd Schnabl, Tobias Goeser, Hans-Michael Steffen, Muenevver Demir
Summary: The study found that BMI was most strongly associated with histological fibrosis in NAFLD patients, while PNPLA3 gene variants, gut bacterial features, and dietary factors were all associated with different histology features.
LIVER INTERNATIONAL
(2021)
Review
Biochemistry & Molecular Biology
Natalia Vallianou, Gerasimos Socrates Christodoulatos, Irene Karampela, Dimitrios Tsilingiris, Faidon Magkos, Theodora Stratigou, Dimitris Kounatidis, Maria Dalamaga
Summary: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, often starting as a benign liver fat accumulation that can progress to non-alcoholic steatohepatitis (NASH) and increase the risk of cirrhosis and hepatocellular carcinoma (HCC). Recent studies have highlighted the role of gut dysbiosis, which can lead to increased gut permeability and the release of toxic bacterial products and proinflammatory cytokines, causing and sustaining inflammation. The composition of the gut microbiota and various metabolites may vary during different stages of NAFLD and among population groups, and further research is needed to determine the causal relationship between gut microbiota profiles and NAFLD in patients. Additionally, multiple metabolites may contribute to the pathogenesis of NAFLD.
Article
Gastroenterology & Hepatology
Munevver Demir, Sonja Lang, Phillipp Hartmann, Yi Duan, Anna Martin, Yukiko Miyamoto, Marina Bondareva, Xinlian Zhang, Yanhan Wang, Philipp Kasper, Corinna Bang, Christoph Roderburg, Frank Tacke, Hans-Michael Steffen, Tobias Goeser, Andrey Kruglov, Lars Eckmann, Peter Starkel, Derrick E. Fouts, Bernd Schnabl
Summary: The study found that the fecal fungal composition of patients with non-alcoholic fatty liver disease (NAFLD) is associated with disease severity. Non-obese NAFLD patients have a distinct fungal ratio in their feces compared to other types of patients. Antifungal treatment in a mouse model can reduce liver damage from steatohepatitis.
JOURNAL OF HEPATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Haripriya Gupta, Byeong-Hyun Min, Raja Ganesan, Yoseph Asmelash Gebru, Satya Priya Sharma, Eunju Park, Sung-Min Won, Jin-Ju Jeong, Su-Been Lee, Min-Gi Cha, Goo-Hyun Kwon, Min-Kyo Jeong, Ji-Ye Hyun, Jung-A Eom, Hee-Jin Park, Sang-Jun Yoon, Mi-Ran Choi, Dong-Joon Kim, Ki-Tae Suk
Summary: Non-alcoholic fatty liver disease (NAFLD) is a significant health threat globally and has attracted attention in the field of liver diseases. It comprises various fatty degenerative disorders in the liver, with complex and multifactor-driven pathophysiology. In addition to viruses, metabolic syndrome, and alcohol, evidence suggests that the microbiome is also associated with the development and progression of NAFLD.
Review
Nutrition & Dietetics
Weifeng Zhu, Ying Zhou, Rong Tsao, Huanhuan Dong, Hua Zhang
Summary: Non-alcoholic fatty liver disease (NAFLD) is a global epidemic, and impaired gut barrier function caused by an unhealthy diet plays a key role in its development. Dietary interventions with resistant starches (RSs) can alter gut microbiota, enhance immune tolerance, and promote the production of microbial metabolites to maintain immune-metabolic homeostasis in the gut-liver axis (GLA). Thus, dietary intervention with RSs may be a promising alternative therapeutic strategy against NAFLD.
FRONTIERS IN NUTRITION
(2022)
Review
Biochemistry & Molecular Biology
Xiang Chen, Menghan Liu, Jun Tang, Ning Wang, Yibin Feng, Haotian Ma
Summary: NAFLD is the most common chronic liver disease affecting global public health at present, and there is a lack of research on its mechanism and therapeutic strategy. The gut-liver axis theory has gradually disclosed the association between polysaccharides and the protective role in NAFLD by affecting multiple interrelated levels such as gut microbiota, metabolites regulation, and intestinal barrier function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Roberta Forlano, Mathuri Sivakumar, Benjamin H. Mullish, Pinelopi Manousou
Summary: NAFLD is an increasingly common liver disease globally, with no approved pharmaceutical treatment available. Manipulating the intestinal microbiome may be a potential therapeutic option for patients with NAFLD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Gastroenterology & Hepatology
Mijra Koning, Hilde Herrema, Max Nieuwdorp, Abraham S. Meijnikman
Summary: Humans have a diverse gut microbiome, consisting of bacteria, fungi, viruses, and archaea. Patients with NAFLD have an altered gut microbiome and compromised gut barrier function. Preclinical studies suggest that adjusting the gut microbiome could be a promising therapeutic strategy for NAFLD. This overview summarizes the current information on both untargeted techniques (such as probiotics and fecal microbiota transplantation) and targeted microbiome-focused therapies (including engineered bacteria, prebiotics, postbiotics, and phages) for the treatment of NAFLD.
Article
Nutrition & Dietetics
Camille Houron, Dragos Ciocan, Nicolas Trainel, Francoise Mercier-Nome, Cindy Hugot, Madeleine Spatz, Gabriel Perlemuter, Anne-Marie Cassard
Summary: The study suggests that pectin plays a positive role in non-alcoholic fatty liver disease (NAFLD) by affecting gut bacteria, with preventive and curative fecal microbiota transfer (FMT) having different mechanisms of action on NAFLD.
Review
Medicine, Research & Experimental
Lijun Luo, Yongchun Chang, Li Sheng
Summary: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide, but its pathogenesis is still unclear. Recent research has shown a close relationship between the intestinal microbiome and NAFLD, and the theory of the gut-liver axis has been proposed. This review focuses on the role of gut bacteria and their components and metabolites in the progression of NAFLD, providing important insights into the pathogenesis, diagnosis, and treatment of this prevalent liver disease.
Article
Biochemistry & Molecular Biology
Xia Liu, Runzhou Sun, Zhaozhen Li, Ruixin Xiao, Pengfei Lv, Xiangrong Sun, Mark A. Olson, Yanling Gong
Summary: Luteolin has been shown to alleviate NAFLD by restoring and repairing the damaged intestinal mucosal barrier and microbiota imbalance, ultimately improving gut health and reducing liver inflammation.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Review
Microbiology
Stephanie L. Rager, Melody Y. Zeng
Summary: There is increasing interest in understanding the interactions between the human gut and microorganisms, and how these interactions affect overall health and disease. The liver, as a vital organ for metabolism, is closely connected to the gut microbial environment through the portal venous system. Although there is extensive research on the gut-liver axis in adults, our understanding of this axis in children, who have unique physiology and gut microbiota, remains limited. This study provides a comprehensive overview of common pediatric hepatobiliary conditions and recent research on the role of gut microbiota in these conditions, as well as the changes in gut microbiota caused by these conditions. The study also explores potential therapeutic approaches that involve modulating the gut microbiota and gut-liver axis to prevent the progression of pediatric liver disease.
Review
Microbiology
Yiming Ni, Mengna Lu, Yuan Xu, Qixue Wang, Xinyi Gu, Ying Li, Tongxi Zhuang, Chenyi Xia, Ting Zhang, Xiao-jun Gou, Mingmei Zhou
Summary: Non-alcoholic fatty liver disease (NAFLD) is a growing global health problem with suboptimal treatments. Bile acids and gut microbiota play crucial roles in the pathogenesis of NAFLD, and investigating these factors may aid in the development of novel drugs.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Nutrition & Dietetics
Qi Zhang, Wenmin Xing, Qiao Wang, Zhan Tang, Yazhen Wang, Wenyan Gao
Summary: The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) has become a significant healthcare burden worldwide. Recent investigations have shown that the gut microbiota plays a crucial role in the progression of NAFLD through the gut-liver axis or gut-brain-liver axis. The composition of the microbiota can be influenced by various factors, including dietary style, nutritional supplements, or exercise. Additionally, microbiota metabolites can impact mitochondrial function and inflammatory response, which are important factors in NAFLD.
FRONTIERS IN NUTRITION
(2022)
Review
Gastroenterology & Hepatology
Alix Bruneau, Adrien Guillot, Frank Tacke
Summary: Cholangiopathies are a heterogeneous class of liver diseases where cholangiocytes are the main targets of liver injury. Available therapies mainly target bile acids and related signaling pathways, but the mechanisms underlying inflammation, ductular reaction, and fibrosis are still poorly understood.
CURRENT OPINION IN GASTROENTEROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Imene Gasmi, Camilia Machou, Aurelie Rodrigues, Arthur Brouillet, Trung Cong Nguyen, Benoit Rousseau, Adrien Guillot, Christophe Rodriguez, Vanessa Demontant, Yeni Ait-Ahmed, Julien Calderaro, Alain Luciani, Jean-Michel Pawlotsky, Fouad Lafdil
Summary: Chronic inflammation plays a key role in the development of primary liver cancers. This study found that long-term exposure of liver progenitor cells (LPCs) to Interleukin (IL)-17 cytokine promotes their transformation into cancer stem cells (CSCs). IL-17-neutralizing strategies can limit CSC occurrence and liver tumor progression through restored-expression of miR-122.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Cell Biology
Alix Bruneau, Jean-Louis Delaunay, Anne-Marie Durand-Schneider, Virginie Vauthier, Amel Ben Saad, Lynda Aoudjehane, Haquima El Mourabit, Romain Morichon, Thomas Falguieres, Jeremie Gautheron, Chantal Housset, Tounsia Ait-Slimane
Summary: This study identifies MRCK alpha and MRLC as novel partners of ABCB4, and shows that they regulate the cell surface expression of ABCB4.
Article
Biochemistry & Molecular Biology
Tobias Puengel, Hanyang Liu, Adrien Guillot, Felix Heymann, Frank Tacke, Moritz Peiseler
Summary: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are chronic liver diseases that can lead to end-stage liver disease and hepatocellular carcinoma (HCC) worldwide. The metabolic syndrome is closely linked to NAFLD, and comorbidities such as type 2 diabetes, obesity, and insulin resistance worsen liver disease, while NAFLD increases cardiovascular risk in affected patients. Therapeutic strategies targeting multiple drug targets or drugs with multiple mechanisms of actions are needed for effective treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Gastroenterology & Hepatology
Adrien Guillot, Frank Tacke
Summary: The liver microenvironment is still not fully understood in terms of its dynamic complexity. A new omics study investigates the spatial distribution of myeloid cells and macrophages in the liver during homeostasis and nonalcoholic fatty liver disease, providing insight into their heterogeneity.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2022)
Article
Multidisciplinary Sciences
Gizem Guenes Guensel, Thomas M. Conlon, Aicha Jeridi, Rinho Kim, Zeynep Ertuez, Niklas J. Lang, Meshal Ansari, Mariia Novikova, Dongsheng Jiang, Maximilian Strunz, Mariia Gaianova, Christine Hollauer, Christina Gabriel, Ilias Angelidis, Sebastian Doll, Jeanine C. Pestoni, Stephanie L. Edelmann, Marlene Sophia Kohlhepp, Adrien Guillot, Kevin Bassler, Hannelore P. Van Eeckhoutte, Oezgecan Kayalar, Nur Konyalilar, Tamara Kanashova, Sophie Rodius, Carolina Ballester-Lopez, Carlos M. Genes Robles, Natalia Smirnova, Markus Rehberg, Charu Agarwal, Ioanna Krikki, Benoit Piavaux, Stijn E. Verleden, Bart Vanaudenaerde, Melanie Koenigshoff, Gunnar Dittmar, Ken R. Bracke, Joachim L. Schultze, Henrik Watz, Oliver Eickelberg, Tobias Stoeger, Gerald Burgstaller, Frank Tacke, Vigo Heissmeyer, Yuval Rinkevich, Hasan Bayram, Herbert B. Schiller, Marcus Conrad, Robert Schneider, Ali Oender Yildirim
Summary: This study demonstrates the role of PRMT7 in regulating the recruitment and pro-inflammatory phenotype of macrophages in chronic obstructive pulmonary disease (COPD). Reduced expression of PRMT7 is associated with decreased recruitment of monocytes to the site of injury and less severe symptoms in mouse models.
NATURE COMMUNICATIONS
(2022)
Article
Biotechnology & Applied Microbiology
Shuai Chen, Xiurong Cai, Yu Liu, Yu Shen, Adrien Guillot, Frank Tacke, Liming Tang, Hanyang Liu
Summary: This study reveals the high infiltration of macrophages (MPs) during the progression of nonalcoholic fatty liver disease (NAFLD). Eight hub genes associated with NAFLD progression are identified, and the potential role of the miR-4715-3p/GSDMD axis in regulating macrophage immunity and indicating fibrosis progression is discovered.
Article
Gastroenterology & Hepatology
Adrien Guillot, Marc Winkler, Milessa Silva Afonso, Abhishek Aggarwal, David Lopez, Hilmar Berger, Marlene S. Kohlhepp, Hanyang Liu, Burcin Ozdirik, Johannes Eschrich, Jing Ma, Moritz Peiseler, Felix Heymann, Swetha Pendem, Sangeetha Mahadevan, Bin Gao, Lauri Diehl, Ruchi Gupta, Frank Tacke
Summary: This study investigates the hepatic immune microenvironment in chronic liver diseases using transcriptomic and histological methods. The findings suggest that the progression of NAFLD/NASH and primary sclerosing cholangitis is characterized by loss of parenchymal areas, accumulation of ductular cells, and infiltration of immune cells.
Article
Biochemistry & Molecular Biology
Jean-Louis Delaunay, Ahmad Elbahnsi, Alix Bruneau, Claire Madry, Anne-Marie Durand-Schneider, Anne Stary, Chantal Housset, Jeremie Gautheron, Isabelle Callebaut, Tounsia Ait-Slimane
Summary: ABCB4 is a hepatocanalicular floppase that plays a role in biliary phosphatidylcholine (PC) secretion. Variations in the ABCB4 gene can cause biliary diseases, including PFIC3. This study demonstrates that ten missense variations in ABCB4 can be rescued by the CFTR potentiator ivacaftor, indicating a potential treatment option for PFIC3 patients with ATP-binding site mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Xiurong Cai, Adrien Guillot, Hanyang Liu
Summary: With high morbidity and mortality, hepatocellular carcinoma (HCC) is a significant and increasing burden globally. The relapse-prone nature and drug resistance of HCC are attributed to various intracellular processes and extracellular interplay, which actively participate in tumor microenvironment remodeling. Cellular senescence, considered as a fail-safe program, plays a crucial role in the progression of chronic inflammatory liver diseases and carcinogenesis. The potential of senescence in affecting anti-cancer strategies is gaining attention in recent studies.
Article
Biochemistry & Molecular Biology
Shuai Chen, Liming Tang, Adrien Guillot, Hanyang Liu
Summary: Nonalcoholic steatohepatitis (NASH), a common chronic liver disease, lacks effective drugs or treatments. Bariatric surgery (BS) is a potential therapy for NASH, showing beneficial effects on liver metabolic diseases. In this study, RNA-sequencing datasets were used to investigate transcriptome variation after one-year BS and diet management in NASH patients. BS led to significant gene expression alterations and reduced stress and immune response compared to diet management. The study identified key genes and SPP1 as a crucial factor in BS-intervened NASH-HCC progression.
Review
Immunology
Xiurong Cai, Frank Tacke, Adrien Guillot, Hanyang Liu
Summary: Biliary epithelial cells, also known as cholangiocytes, form a barrier between intra- and extrahepatic bile ducts and modulate bile composition and transportation. In hepatobiliary diseases, bile duct injury leads to alterations in cholangiocyte phenotypes and their release of cytokines, which contribute to ductular cell proliferation, inflammation, fibrosis, and carcinogenesis. This review summarizes recent insights into the role of cholangiocytes in liver injury-regeneration, inflammation, fibrosis, and malignant transformation.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Marlene Sophia Kohlhepp, Hanyang Liu, Frank Tacke, Adrien Guillot
Summary: Chronic liver diseases, including NAFLD, can lead to liver fibrosis and cirrhosis, as well as increase the risk of liver cancer. Monocytes and macrophages play a crucial role in the initiation and progression of chronic liver diseases. Recent studies have revealed the diverse functions of liver macrophages, including inflammation modulation, tissue repair promotion, and even tumor cell proliferation. Targeting liver macrophages could be a promising therapeutic approach for the treatment of liver diseases. In this review, the multifaceted and contradictory roles of macrophages in chronic liver diseases, particularly NAFLD/NASH and HCC, are discussed, along with potential therapeutic strategies.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Multidisciplinary Sciences
Moritz Peiseler, Bruna Araujo David, Joel Zindel, Bas G. J. Surewaard, Woo-Yong Lee, Felix Heymann, Ysbrand Nusse, Fernanda V. S. Castanheira, Raymond Shim, Adrien Guillot, Alix Bruneau, Jawairia Atif, Catia Perciani, Christina Ohland, Priyanka Ganguli Mukherjee, Annika Niehrs, Roland Thuenauer, Marcus Altfeld, Mathias Amrein, Zhaoyuan Liu, Paul M. K. Gordon, Kathy McCoy, Justin Deniset, Sonya MacParland, Florent Ginhoux, Frank Tacke, Paul Kubes
Summary: Liver fibrosis disrupts the interaction between Kupffer cells and parenchymal cells, leading to a decrease in bacterial clearance ability. Commensal bacteria stimulate the recruitment of monocytes through CD44 to form multinucleated cell aggregates (syncytia) in a distinct vascular compartment. These syncytia display enhanced bacterial capture ability and may represent an antimicrobial defense mechanism that evolved with fibrosis.
Article
Medicine, Research & Experimental
Dechun Feng, Xiaogang Xiang, Yukun Guan, Adrien Guillot, Hongkun Lu, Chingwen Chang, Yong He, Hua Wang, Hongna Pan, Cynthia Ju, Sean P. Colgan, Frank Tacke, Xin Wei Wang, George Kunos, Bin Gao
Summary: Monocyte-derived macrophages (MoMFs) are rapidly recruited to and encapsulated necrotic areas during liver injury, playing a key role in repairing necrotic lesions. They induce cell death-resistant hepatocytes to form a protective capsule and participate in necrotic tissue removal and liver repair. MoMFs also activate hepatic stellate cells to eliminate necrotic lesions through α-smooth muscle actin expression.
JOURNAL OF CLINICAL INVESTIGATION
(2023)