{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T21:23:25Z","timestamp":1788989005411,"version":"build-2803163510"},"reference-count":155,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AIRC","award":["IG 2020\u2014ID 25187"],"award-info":[{"award-number":["IG 2020\u2014ID 25187"]}]},{"name":"AIRC","award":["PNRR\u2014M4C2-I1.3 Project PE_00000019"],"award-info":[{"award-number":["PNRR\u2014M4C2-I1.3 Project PE_00000019"]}]},{"name":"AIRC","award":["J33C22002920006"],"award-info":[{"award-number":["J33C22002920006"]}]},{"name":"EUROPEAN UNION\u2014NEXTGENERATIONEU through the Italian Ministry of University and Research","award":["IG 2020\u2014ID 25187"],"award-info":[{"award-number":["IG 2020\u2014ID 25187"]}]},{"name":"EUROPEAN UNION\u2014NEXTGENERATIONEU through the Italian Ministry of University and Research","award":["PNRR\u2014M4C2-I1.3 Project PE_00000019"],"award-info":[{"award-number":["PNRR\u2014M4C2-I1.3 Project PE_00000019"]}]},{"name":"EUROPEAN UNION\u2014NEXTGENERATIONEU through the Italian Ministry of University and Research","award":["J33C22002920006"],"award-info":[{"award-number":["J33C22002920006"]}]},{"name":"CUP of Institution","award":["IG 2020\u2014ID 25187"],"award-info":[{"award-number":["IG 2020\u2014ID 25187"]}]},{"name":"CUP of Institution","award":["PNRR\u2014M4C2-I1.3 Project PE_00000019"],"award-info":[{"award-number":["PNRR\u2014M4C2-I1.3 Project PE_00000019"]}]},{"name":"CUP of Institution","award":["J33C22002920006"],"award-info":[{"award-number":["J33C22002920006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is a heterogeneous tumor associated with several risk factors, with non-alcoholic fatty liver disease (NAFLD) emerging as an important cause of liver tumorigenesis. Due to the obesity epidemics, the occurrence of NAFLD has significantly increased with nearly 30% prevalence worldwide. HCC often arises in the background of chronic liver disease (CLD), such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Gut microbiome (GM) alterations have been linked to NAFLD progression and HCC development, with several investigations reporting a crucial role for the gut\u2013liver axis and microbial metabolites in promoting CLD. Moreover, the GM affects liver homeostasis, energy status, and the immune microenvironment, influencing the response to immunotherapy with interesting therapeutic implications. In this review, we summarize the main changes in the GM and derived metabolites (e.g., short-chain fatty acids and bile acids) occurring in HCC patients and influencing NAFLD progression, emphasizing their potential as early diagnostic biomarkers and prognostic tools. We discuss the weight loss effects of diet-based interventions and healthy lifestyles for the treatment of NAFLD patients, highlighting their impact on the restoration of the intestinal barrier and GM structure. We also describe encouraging preclinical findings on the modulation of GM to improve liver functions in CLD, boost the antitumor immune response (e.g., probiotic supplementations or anti-hypercholesterolemic drug treatment), and ultimately delay NAFLD progression to HCC. The development of safe and effective strategies that target the gut\u2013liver axis holds promise for liver cancer prevention and treatment, especially if personalized options will be considered.<\/jats:p>","DOI":"10.3390\/cells14020084","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T09:54:27Z","timestamp":1736416467000},"page":"84","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Gut Microbiome Modulation in Hepatocellular Carcinoma: Preventive Role in NAFLD\/NASH Progression and Potential Applications in Immunotherapy-Based Strategies"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0679-6075","authenticated-orcid":false,"given":"Elisa","family":"Monti","sequence":"first","affiliation":[{"name":"Department for Life Quality Studies, University of Bologna, Corso d\u2019Augusto 237, 47921 Rimini, Italy"},{"name":"Centre for Applied Biomedical Research\u2014CRBA, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Vianello","sequence":"additional","affiliation":[{"name":"Department for Life Quality Studies, University of Bologna, Corso d\u2019Augusto 237, 47921 Rimini, Italy"},{"name":"Centre for Applied Biomedical Research\u2014CRBA, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Leoni","sequence":"additional","affiliation":[{"name":"Department for Life Quality Studies, University of Bologna, Corso d\u2019Augusto 237, 47921 Rimini, Italy"},{"name":"Centre for Applied Biomedical Research\u2014CRBA, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4533-9134","authenticated-orcid":false,"given":"Giuseppe","family":"Galvani","sequence":"additional","affiliation":[{"name":"Department for Life Quality Studies, University of Bologna, Corso d\u2019Augusto 237, 47921 Rimini, Italy"},{"name":"Centre for Applied Biomedical Research\u2014CRBA, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Lippolis","sequence":"additional","affiliation":[{"name":"Department for Life Quality Studies, University of Bologna, Corso d\u2019Augusto 237, 47921 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2136-9558","authenticated-orcid":false,"given":"Federica","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2455-6624","authenticated-orcid":false,"given":"Sara","family":"Roggiani","sequence":"additional","affiliation":[{"name":"Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy"},{"name":"Human Microbiomics Unit, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Stefanelli","sequence":"additional","affiliation":[{"name":"Department for Life Quality Studies, University of Bologna, Corso d\u2019Augusto 237, 47921 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2345-9482","authenticated-orcid":false,"given":"Silvia","family":"Turroni","sequence":"additional","affiliation":[{"name":"Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy"},{"name":"IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4302-4411","authenticated-orcid":false,"given":"Francesca","family":"Fornari","sequence":"additional","affiliation":[{"name":"Department for Life Quality Studies, University of Bologna, Corso d\u2019Augusto 237, 47921 Rimini, Italy"},{"name":"IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S2468-1253(22)00165-0","article-title":"The Prevalence and Incidence of NAFLD Worldwide: A Systematic Review and Meta-Analysis","volume":"7","author":"Riazi","year":"2022","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/s41571-023-00825-3","article-title":"Global Trends in Hepatocellular Carcinoma Epidemiology: Implications for Screening, Prevention and Therapy","volume":"20","author":"Singal","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.jhep.2018.05.036","article-title":"Modeling NAFLD Disease Burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the Period 2016\u20132030","volume":"69","author":"Estes","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.jhep.2021.11.018","article-title":"BCLC Strategy for Prognosis Prediction and Treatment Recommendation: The 2022 Update","volume":"76","author":"Reig","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s41577-020-0306-5","article-title":"A Guide to Cancer Immunotherapy: From T Cell Basic Science to Clinical Practice","volume":"20","author":"Waldman","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1200\/JCO.23.02745","article-title":"Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update","volume":"40","author":"Gordan","year":"2024","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/s41586-021-03362-0","article-title":"NASH Limits Anti-Tumour Surveillance in Immunotherapy-Treated HCC","volume":"592","author":"Pfister","year":"2021","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Fang, J., Yu, C.-H., Li, X.-J., Yao, J.-M., Fang, Z.-Y., Yoon, S.-H., and Yu, W.-Y. (2022). Gut Dysbiosis in Nonalcoholic Fatty Liver Disease: Pathogenesis, Diagnosis, and Therapeutic Implications. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.997018"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"441","DOI":"10.4161\/gmic.29599","article-title":"The Role of the Gut Microbiome in the Development and Progression of Liver Cirrhosis and Hepatocellular Carcinoma","volume":"5","author":"Roderburg","year":"2014","journal-title":"Gut Microbes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2240031","DOI":"10.1080\/19490976.2023.2240031","article-title":"Unveiling the Complex Relationship between Gut Microbiota and Liver Cancer: Opportunities for Novel Therapeutic Interventions","volume":"15","author":"Rajapakse","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1038\/s43018-021-00251-3","article-title":"Chronic Liver Disease Enables Gut Enterococcus Faecalis Colonization to Promote Liver Carcinogenesis","volume":"2","author":"Iida","year":"2021","journal-title":"Nat. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3964","DOI":"10.1038\/s41467-022-31312-5","article-title":"Imbalanced Gut Microbiota Fuels Hepatocellular Carcinoma Development by Shaping the Hepatic Inflammatory Microenvironment","volume":"13","author":"Schneider","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.ccell.2018.03.015","article-title":"The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy","volume":"33","author":"Gopalakrishnan","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/j.tem.2024.06.003","article-title":"Understanding Gut Dysbiosis for Hepatocellular Carcinoma Diagnosis and Treatment","volume":"35","author":"Yu","year":"2024","journal-title":"Trends Endocrinol. Metab. TEM"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/j.cmet.2022.09.017","article-title":"Gut-Liver Axis: Pathophysiological Concepts and Clinical Implications","volume":"34","author":"Tilg","year":"2022","journal-title":"Cell Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/s41579-023-00904-3","article-title":"The Gut\u2013Liver Axis and Gut Microbiota in Health and Liver Disease","volume":"21","author":"Hsu","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/s41575-018-0011-z","article-title":"The Gut-Liver Axis and the Intersection with the Microbiome","volume":"15","author":"Tripathi","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100344","DOI":"10.1016\/j.jhepr.2021.100344","article-title":"Ablation of Liver Fxr Results in an Increased Colonic Mucus Barrier in Mice","volume":"3","author":"Ijssennagger","year":"2021","journal-title":"JHEP Rep. Innov. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9066","DOI":"10.1073\/pnas.1219451110","article-title":"Cross-Talk between Akkermansia Muciniphila and Intestinal Epithelium Controls Diet-Induced Obesity","volume":"110","author":"Everard","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2331460","DOI":"10.1080\/19490976.2024.2331460","article-title":"Breaking the Barriers: The Role of Gut Homeostasis in Metabolic-Associated Steatotic Liver Disease (MASLD)","volume":"16","author":"Cubero","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/j.jhep.2019.08.005","article-title":"Microbiota-Driven Gut Vascular Barrier Disruption Is a Prerequisite for Non-Alcoholic Steatohepatitis Development","volume":"71","author":"Mouries","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.jhep.2019.08.016","article-title":"Gut Microbiome in HCC\u2014Mechanisms, Diagnosis and Therapy","volume":"72","author":"Schwabe","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.ccr.2012.02.007","article-title":"Promotion of Hepatocellular Carcinoma by the Intestinal Microbiota and TLR4","volume":"21","author":"Dapito","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1002\/ptr.7434","article-title":"Nimbolide Attenuates Gut Dysbiosis and Prevents Bacterial Translocation by Improving Intestinal Barrier Integrity and Ameliorating Inflammation in Hepatocellular Carcinoma","volume":"36","author":"Ram","year":"2022","journal-title":"Phytother. Res. PTR"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.jhep.2012.06.011","article-title":"Profound Impact of Gut Homeostasis on Chemically-Induced pro-Tumorigenic Inflammation and Hepatocarcinogenesis in Rats","volume":"57","author":"Zhang","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wang, X., Fang, Y., Liang, W., Cai, Y., Wong, C.C., Wang, J., Wang, N., Lau, H.C.-H., Jiao, Y., and Zhou, X. (Nat. Microbiol., 2025). Gut-Liver Translocation of Pathogen Klebsiella Pneumoniae Promotes Hepatocellular Carcinoma in Mice, Nat. Microbiol., online ahead of print.","DOI":"10.1038\/s41564-024-01890-9"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.lfs.2018.08.017","article-title":"Gut Inflammation Exacerbates Hepatic Injury in the High-Fat Diet Induced NAFLD Mouse: Attention to the Gut-Vascular Barrier Dysfunction","volume":"209","author":"Cheng","year":"2018","journal-title":"Life Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wang, Y.-L., Liu, C., Yang, Y.-Y., Zhang, L., Guo, X., Niu, C., Zhang, N.-P., Ding, J., and Wu, J. (2024). Dynamic Changes of Gut Microbiota in Mouse Models of Metabolic Dysfunction-Associated Steatohepatitis and Its Transition to Hepatocellular Carcinoma. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol., 38.","DOI":"10.1096\/fj.202400573RR"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.jhep.2017.12.025","article-title":"Effects of the Gut-Liver Axis on Ischaemia-Mediated Hepatocellular Carcinoma Recurrence in the Mouse Liver","volume":"68","author":"Orci","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"111188","DOI":"10.1016\/j.humimm.2024.111188","article-title":"Exploring the Modulation of TLR4 and Its Associated ncRNAs in Cancer Immunopathogenesis, with an Emphasis on the Therapeutic Implications and Mechanisms Underlying Drug Resistance","volume":"86","author":"Alshahrani","year":"2025","journal-title":"Hum. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1038\/s12276-023-01050-9","article-title":"MicroRNA: Trends in Clinical Trials of Cancer Diagnosis and Therapy Strategies","volume":"55","author":"Kim","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1136\/gutjnl-2017-315084","article-title":"Gut Microbiome Analysis as a Tool towards Targeted Non-Invasive Biomarkers for Early Hepatocellular Carcinoma","volume":"68","author":"Ren","year":"2019","journal-title":"Gut"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1136\/gutjnl-2015-309800","article-title":"Metagenomic Analysis of Faecal Microbiome as a Tool towards Targeted Non-Invasive Biomarkers for Colorectal Cancer","volume":"66","author":"Yu","year":"2017","journal-title":"Gut"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/hep.30036","article-title":"Hepatocellular Carcinoma Is Associated With Gut Microbiota Profile and Inflammation in Nonalcoholic Fatty Liver Disease","volume":"69","author":"Ponziani","year":"2019","journal-title":"Hepatology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/s41467-020-20422-7","article-title":"Gut Microbiota Impact on the Peripheral Immune Response in Non-Alcoholic Fatty Liver Disease Related Hepatocellular Carcinoma","volume":"12","author":"Behary","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e00182","DOI":"10.1097\/HC9.0000000000000182","article-title":"A Gut Bacterial Signature in Blood and Liver Tissue Characterizes Cirrhosis and Hepatocellular Carcinoma","volume":"7","author":"Effenberger","year":"2023","journal-title":"Hepatol. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/s41586-020-2881-9","article-title":"Host Variables Confound Gut Microbiota Studies of Human Disease","volume":"587","author":"Sklar","year":"2020","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6528","DOI":"10.1038\/ncomms7528","article-title":"Gut Microbiome Development along the Colorectal Adenoma\u2013Carcinoma Sequence","volume":"6","author":"Feng","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1016\/j.transproceed.2016.01.077","article-title":"Profile of Gut Microbiota Associated With the Presence of Hepatocellular Cancer in Patients With Liver Cirrhosis","volume":"48","author":"Wronka","year":"2016","journal-title":"Transplant. Proc."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Pallozzi, M., De Gaetano, V., Di Tommaso, N., Cerrito, L., Santopaolo, F., Stella, L., Gasbarrini, A., and Ponziani, F.R. (2024). Role of Gut Microbial Metabolites in the Pathogenesis of Primary Liver Cancers. Nutrients, 16.","DOI":"10.3390\/nu16142372"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41574-019-0156-z","article-title":"Gut Microbial Metabolites in Obesity, NAFLD and T2DM","volume":"15","author":"Canfora","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1002\/hep.29892","article-title":"Link between Gut-Microbiome Derived Metabolite and Shared Gene-Effects with Hepatic Steatosis and Fibrosis in NAFLD","volume":"68","author":"Caussy","year":"2018","journal-title":"Hepatology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"101119","DOI":"10.1016\/j.jhepr.2024.101119","article-title":"Metabolomics Biomarkers of Hepatocellular Carcinoma in a Prospective Cohort of Patients with Cirrhosis","volume":"6","author":"Sanchez","year":"2024","journal-title":"JHEP Rep. Innov. Hepatol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Li, X., Yi, Y., Wu, T., Chen, N., Gu, X., Xiang, L., Jiang, Z., Li, J., and Jin, H. (2023). Integrated Microbiome and Metabolome Analysis Reveals the Interaction between Intestinal Flora and Serum Metabolites as Potential Biomarkers in Hepatocellular Carcinoma Patients. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1170748"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41577-024-01014-8","article-title":"Short-Chain Fatty Acids: Linking Diet, the Microbiome and Immunity","volume":"24","author":"Mann","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1097\/HEP.0000000000000047","article-title":"Gut Microbial Metabolite Butyrate Improves Anticancer Therapy by Regulating Intracellular Calcium Homeostasis","volume":"78","author":"Che","year":"2023","journal-title":"Hepatology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1002\/hep.32449","article-title":"Gut Microbiota-Derived Short-Chain Fatty Acids Regulate Group 3 Innate Lymphoid Cells in HCC","volume":"77","author":"Hu","year":"2023","journal-title":"Hepatology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2297846","DOI":"10.1080\/19490976.2023.2297846","article-title":"Thetaiotaomicron-Derived Acetic Acid Modulate Immune Microenvironment and Tumor Growth in Hepatocellular Carcinoma","volume":"16","author":"Ma","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1016\/j.cmet.2023.09.009","article-title":"High Dietary Fructose Promotes Hepatocellular Carcinoma Progression by Enhancing O-GlcNAcylation via Microbiota-Derived Acetate","volume":"35","author":"Zhou","year":"2023","journal-title":"Cell Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3892\/ijo.2024.5632","article-title":"Butyrate as a Promising Therapeutic Target in Cancer: From Pathogenesis to Clinic (Review)","volume":"64","author":"Sun","year":"2024","journal-title":"Int. J. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cmet.2016.05.005","article-title":"Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism","volume":"24","author":"Sayin","year":"2016","journal-title":"Cell Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrgastro.2017.119","article-title":"Bile Acid-Microbiota Crosstalk in Gastrointestinal Inflammation and Carcinogenesis","volume":"15","author":"Jia","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jhep.2024.09.032","article-title":"Bile Acid Metabolism and Signalling in Liver Disease","volume":"82","author":"Fuchs","year":"2025","journal-title":"J. Hepatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41579-022-00805-x","article-title":"Bile Acids and the Gut Microbiota: Metabolic Interactions and Impacts on Disease","volume":"21","author":"Collins","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_56","first-page":"144","article-title":"Bile Acids, Gut Microbiota, and Therapeutic Insights in Hepatocellular Carcinoma","volume":"21","author":"Song","year":"2023","journal-title":"Cancer Biol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1002\/hep.32568","article-title":"Metabolic Reprogramming of the Intestinal Microbiome with Functional Bile Acid Changes Underlie the Development of NAFLD","volume":"76","author":"Smirnova","year":"2022","journal-title":"Hepatology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nature12347","article-title":"Obesity-Induced Gut Microbial Metabolite Promotes Liver Cancer through Senescence Secretome","volume":"499","author":"Yoshimoto","year":"2013","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"9925","DOI":"10.18632\/oncotarget.24066","article-title":"Bile Acid Metabolism Regulated by the Gut Microbiota Promotes Non-Alcoholic Steatohepatitis-Associated Hepatocellular Carcinoma in Mice","volume":"9","author":"Yamada","year":"2018","journal-title":"Oncotarget"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"eaan5931","DOI":"10.1126\/science.aan5931","article-title":"Gut Microbiome-Mediated Bile Acid Metabolism Regulates Liver Cancer via NKT Cells","volume":"360","author":"Ma","year":"2018","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1016\/j.jhep.2021.01.028","article-title":"STARD1 Promotes NASH-Driven HCC by Sustaining the Generation of Bile Acids through the Alternative Mitochondrial Pathway","volume":"74","author":"Vallejo","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2172671","DOI":"10.1080\/19490976.2023.2172671","article-title":"Bile Acids as Modulators of Gut Microbiota Composition and Function","volume":"15","author":"Larabi","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global Burden of NAFLD and NASH: Trends, Predictions, Risk Factors and Prevention","volume":"15","author":"Younossi","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/nrgastro.2013.183","article-title":"NAFLD, NASH and Liver Cancer","volume":"10","author":"Michelotti","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/nrgastro.2016.147","article-title":"NAFLD and Diabetes Mellitus","volume":"14","author":"Tilg","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1053\/j.gastro.2019.11.312","article-title":"MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease","volume":"158","author":"Eslam","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","article-title":"The Global Epidemiology of Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH): A Systematic Review","volume":"77","author":"Younossi","year":"2023","journal-title":"Hepatology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1053\/j.gastro.2005.04.014","article-title":"The Natural History of Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study","volume":"129","author":"Adams","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The Multiple-Hit Pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1016\/j.jhep.2014.11.034","article-title":"Evidence of NAFLD Progression from Steatosis to Fibrosing-Steatohepatitis Using Paired Biopsies: Implications for Prognosis and Clinical Management","volume":"62","author":"McPherson","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1002\/hep.27368","article-title":"Fibrosis Stage Is the Strongest Predictor for Disease-Specific Mortality in NAFLD after up to 33 Years of Follow-Up","volume":"61","author":"Ekstedt","year":"2015","journal-title":"Hepatology"},{"key":"ref_72","first-page":"1342","article-title":"Association between Nonalcoholic Fatty Liver Disease and Risk for Hepatocellular Cancer, Based on Systematic Review","volume":"10","author":"White","year":"2012","journal-title":"Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1053\/j.gastro.2018.08.024","article-title":"Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease","volume":"155","author":"Kanwal","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1002\/hep.31014","article-title":"Effect of Metabolic Traits on the Risk of Cirrhosis and Hepatocellular Cancer in Nonalcoholic Fatty Liver Disease","volume":"71","author":"Kanwal","year":"2020","journal-title":"Hepatology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1002\/hep.28368","article-title":"Clinical Patterns of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease: A Multicenter Prospective Study","volume":"63","author":"Piscaglia","year":"2016","journal-title":"Hepatology"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Motta, B.M., Masarone, M., Torre, P., and Persico, M. (2023). From Non-Alcoholic Steatohepatitis (NASH) to Hepatocellular Carcinoma (HCC): Epidemiology, Incidence, Predictions, Risk Factors, and Prevention. Cancers, 15.","DOI":"10.20944\/preprints202310.1078.v1"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/s41586-024-07372-6","article-title":"Periportal Macrophages Protect against Commensal-Driven Liver Inflammation","volume":"629","author":"Miyamoto","year":"2024","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2223330","DOI":"10.1080\/19490976.2023.2223330","article-title":"Faecal Microbiota Transplantation Affects Liver DNA Methylation in Non-Alcoholic Fatty Liver Disease: A Multi-Omics Approach","volume":"15","author":"Mak","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Pirola, C.J., Salatino, A., Quintanilla, M.F., Casta\u00f1o, G.O., Garaycoechea, M., and Sookoian, S. (2022). The Influence of Host Genetics on Liver Microbiome Composition in Patients with NAFLD. EBioMedicine, 76.","DOI":"10.1016\/j.ebiom.2022.103858"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1002\/hep.32705","article-title":"Enhanced Mitochondrial Activity Reshapes a Gut Microbiota Profile That Delays NASH Progression","volume":"77","author":"Porras","year":"2023","journal-title":"Hepatology"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Huang, F., Lyu, B., Xie, F., Li, F., Xing, Y., Han, Z., Lai, J., Ma, J., Zou, Y., and Zeng, H. (2024). From Gut to Liver: Unveiling the Differences of Intestinal Microbiota in NAFL and NASH Patients. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1366744"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.humic.2018.01.001","article-title":"Gut Microbiota Diversity According to Dietary Habits and Geographical Provenance","volume":"7\u20138","author":"Senghor","year":"2018","journal-title":"Hum. Microbiome J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1038\/s41591-018-0164-x","article-title":"Regional Variation Limits Applications of Healthy Gut Microbiome Reference Ranges and Disease Models","volume":"24","author":"He","year":"2018","journal-title":"Nat. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1126\/science.1224203","article-title":"The Application of Ecological Theory toward an Understanding of the Human Microbiome","volume":"336","author":"Costello","year":"2012","journal-title":"Science"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1080\/19490976.2019.1681861","article-title":"Lower Gut Microbiome Diversity and Higher Abundance of Proinflammatory Genus Collinsella Are Associated with Biopsy-Proven Nonalcoholic Steatohepatitis","volume":"11","author":"Astbury","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Saga, K., Iwashita, Y., Hidano, S., Aso, Y., Isaka, K., Kido, Y., Tada, K., Takayama, H., Masuda, T., and Hirashita, T. (2018). Secondary Unconjugated Bile Acids Induce Hepatic Stellate Cell Activation. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19103043"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1194\/jlr.M062653","article-title":"Deoxycholic Acid Modulates Cell Death Signaling through Changes in Mitochondrial Membrane Properties","volume":"56","author":"Sousa","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e000139","DOI":"10.1136\/bmjgast-2017-000139","article-title":"Efficacy of Dietary and Physical Activity Intervention in Non-Alcoholic Fatty Liver Disease: A Systematic Review","volume":"4","author":"Kenneally","year":"2017","journal-title":"BMJ Open Gastroenterol."},{"key":"ref_89","first-page":"1672","article-title":"Higher Adherence to Plant-Based Diets Are Associated with Lower Likelihood of Fatty Liver","volume":"38","author":"Mazidi","year":"2019","journal-title":"Clin. Nutr. Edinb. Scotl."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1038\/s41591-023-02603-1","article-title":"Resmetirom for Nonalcoholic Fatty Liver Disease: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial","volume":"29","author":"Harrison","year":"2023","journal-title":"Nat. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1056\/NEJMoa2309000","article-title":"A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis","volume":"390","author":"Harrison","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1053\/j.gastro.2012.04.001","article-title":"The Diagnosis and Management of Non-Alcoholic Fatty Liver Disease: Practice Guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology","volume":"142","author":"Chalasani","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), and European Association for the Study of Obesity (EASO) (2016). EASL\u2013EASD\u2013EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease. Diabetologia, 59, 1121\u20131140.","DOI":"10.1007\/s00125-016-3902-y"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/hep.23276","article-title":"Randomized Controlled Trial Testing the Effects of Weight Loss on Nonalcoholic Steatohepatitis","volume":"51","author":"Promrat","year":"2010","journal-title":"Hepatology"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Cheng, S., Ge, J., Zhao, C., Le, S., Yang, Y., Ke, D., Wu, N., Tan, X., Zhang, X., and Du, X. (2017). Effect of Aerobic Exercise and Diet on Liver Fat in Pre-Diabetic Patients with Non-Alcoholic-Fatty-Liver-Disease: A Randomized Controlled Trial. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-16159-x"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1038\/s41467-022-29968-0","article-title":"A Randomized Controlled Trial for Response of Microbiome Network to Exercise and Diet Intervention in Patients with Nonalcoholic Fatty Liver Disease","volume":"13","author":"Cheng","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Calabrese, F.M., Disciglio, V., Franco, I., Sorino, P., Bonfiglio, C., Bianco, A., Campanella, A., Lippolis, T., Pesole, P.L., and Polignano, M. (2022). A Low Glycemic Index Mediterranean Diet Combined with Aerobic Physical Activity Rearranges the Gut Microbiota Signature in NAFLD Patients. Nutrients, 14.","DOI":"10.3390\/nu14091773"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Krawczyk, M., Maciejewska, D., Ryterska, K., Czerwi\u0144ka-Rogowska, M., Jamio\u0142-Milc, D., Skonieczna-\u017bydecka, K., Milkiewicz, P., Raszeja-Wyszomirska, J., and Stachowska, E. (2018). Gut Permeability Might Be Improved by Dietary Fiber in Individuals with Nonalcoholic Fatty Liver Disease (NAFLD) Undergoing Weight Reduction. Nutrients, 10.","DOI":"10.3390\/nu10111793"},{"key":"ref_99","first-page":"678","article-title":"Adherence to the Mediterranean Diet Is Associated with the Severity of Non-Alcoholic Fatty Liver Disease","volume":"33","author":"Kontogianni","year":"2014","journal-title":"Clin. Nutr. Edinb. Scotl."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Stachowska, E., Portincasa, P., Jamio\u0142-Milc, D., Maciejewska-Markiewicz, D., and Skonieczna-\u017bydecka, K. (2020). The Relationship between Prebiotic Supplementation and Anthropometric and Biochemical Parameters in Patients with NAFLD-A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients, 12.","DOI":"10.3390\/nu12113460"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.14309\/ajg.0000000000001885","article-title":"A Freshwater Fish-Based Diet Alleviates Liver Steatosis by Modulating Gut Microbiota and Metabolites: A Clinical Randomized Controlled Trial in Chinese Participants With Nonalcoholic Fatty Liver Disease","volume":"117","author":"He","year":"2022","journal-title":"Am. J. Gastroenterol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"\u0160m\u00edd, V., Dvo\u0159\u00e1k, K., Stehnov\u00e1, K., Strnad, H., Rubert, J., St\u0159\u00edtesk\u00fd, J., Sta\u0148kov\u00e1, B., Str\u00e1nsk\u00e1, M., Haj\u0161lov\u00e1, J., and Br\u016fha, R. (2023). The Ameliorating Effects of N-3 Polyunsaturated Fatty Acids on Liver Steatosis Induced by a High-Fat Methionine Choline-Deficient Diet in Mice. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417226"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/j.jhep.2011.08.018","article-title":"Omega-3 Supplementation and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis","volume":"56","author":"Parker","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2390164","DOI":"10.1080\/19490976.2024.2390164","article-title":"Time-Restricted Feeding Ameliorates Non-Alcoholic Fatty Liver Disease through Modulating Hepatic Nicotinamide Metabolism via Gut Microbiota Remodeling","volume":"16","author":"Feng","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2221450","DOI":"10.1080\/19490976.2023.2221450","article-title":"Resynchronized Rhythmic Oscillations of Gut Microbiota Drive Time-Restricted Feeding Induced Nonalcoholic Steatohepatitis Alleviation","volume":"15","author":"Xia","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.cmet.2017.08.019","article-title":"Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota","volume":"26","author":"Li","year":"2017","journal-title":"Cell Metab."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e2200595","DOI":"10.1002\/mnfr.202200595","article-title":"Intermittent Fasting Alleviates Non-Alcoholic Steatohepatitis by Regulating Bile Acid Metabolism and Promoting Fecal Bile Acid Excretion in High-Fat and High-Cholesterol Diet Fed Mice","volume":"67","author":"Lin","year":"2023","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1097\/HEP.0000000000000330","article-title":"Intermittent Fasting-the Future Treatment in NASH Patients?","volume":"78","author":"Minciuna","year":"2023","journal-title":"Hepatology"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Ahn, S.B., Jun, D.W., Kang, B.-K., Lim, J.H., Lim, S., and Chung, M.-J. (2019). Randomized, Double-Blind, Placebo-Controlled Study of a Multispecies Probiotic Mixture in Nonalcoholic Fatty Liver Disease. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-42059-3"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1053\/j.gastro.2020.01.031","article-title":"Synbiotics Alter Fecal Microbiomes, But Not Liver Fat or Fibrosis, in a Randomized Trial of Patients With Nonalcoholic Fatty Liver Disease","volume":"158","author":"Scorletti","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"107398","DOI":"10.1016\/j.phrs.2024.107398","article-title":"The Effect of Synbiotics on Liver Enzymes, Obesity Indices, Blood Pressure, Lipid Profile, and Inflammation in Patients with Non-Alcoholic Fatty Liver: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"208","author":"Musazadeh","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/19490976.2021.1927633","article-title":"Gut Akkermansia Muciniphila Ameliorates Metabolic Dysfunction-Associated Fatty Liver Disease by Regulating the Metabolism of L-Aspartate via Gut-Liver Axis","volume":"13","author":"Rao","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nm.4236","article-title":"A Purified Membrane Protein from Akkermansia Muciniphila or the Pasteurized Bacterium Improves Metabolism in Obese and Diabetic Mice","volume":"23","author":"Plovier","year":"2017","journal-title":"Nat. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/s41591-019-0495-2","article-title":"Supplementation with Akkermansia Muciniphila in Overweight and Obese Human Volunteers: A Proof-of-Concept Exploratory Study","volume":"25","author":"Depommier","year":"2019","journal-title":"Nat. Med."},{"key":"#cr-split#-ref_115.1","unstructured":"EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck, D., Bohn, T., Castenmiller, J., De Henauw, S., Hirsch-Ernst, K.I., Maciuk, A., Mangelsdorf, I., McArdle, H.J., and Naska, A. (2021). Safety of Pasteurised Akkermansia Muciniphila as a Novel Food Pursuant to Regulation"},{"key":"#cr-split#-ref_115.2","unstructured":"(EU) 2015\/2283. EFSA J. Eur. Food Saf. Auth., 19, e06780."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Mijangos-Trejo, A., Nu\u00f1o-Lambarri, N., Barbero-Becerra, V., Uribe-Esquivel, M., Vidal-Cevallos, P., and Ch\u00e1vez-Tapia, N. (2023). Prebiotics and Probiotics: Therapeutic Tools for Nonalcoholic Fatty Liver Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914918"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Yadegar, A., Bar-Yoseph, H., Monaghan, T.M., Pakpour, S., Severino, A., Kuijper, E.J., Smits, W.K., Terveer, E.M., Neupane, S., and Nabavi-Rad, A. (2024). Fecal Microbiota Transplantation: Current Challenges and Future Landscapes. Clin. Microbiol. Rev., 37.","DOI":"10.1128\/cmr.00060-22"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1002\/hep.29646","article-title":"Restoration of a Healthy Intestinal Microbiota Normalizes Portal Hypertension in a Rat Model of Nonalcoholic Steatohepatitis","volume":"67","author":"Raurell","year":"2018","journal-title":"Hepatology"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Zhou, D., Pan, Q., Shen, F., Cao, H., Ding, W., Chen, Y., and Fan, J. (2017). Total Fecal Microbiota Transplantation Alleviates High-Fat Diet-Induced Steatohepatitis in Mice via Beneficial Regulation of Gut Microbiota. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-01751-y"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Xue, L., Deng, Z., Luo, W., He, X., and Chen, Y. (2022). Effect of Fecal Microbiota Transplantation on Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.759306"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1002\/hep4.1601","article-title":"Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis","volume":"4","author":"Witjes","year":"2020","journal-title":"Hepatol. Commun."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1056\/NEJMoa1205037","article-title":"Duodenal Infusion of Donor Feces for Recurrent Clostridium Difficile","volume":"368","author":"Vrieze","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1053\/j.gastro.2017.01.028","article-title":"The AGA\u2019s Fecal Microbiota Transplantation National Registry: An Important Step Toward Understanding Risks and Benefits of Microbiota Therapeutics","volume":"152","author":"Kelly","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/TP.0000000000002484","article-title":"Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: Implications for Liver Transplantation","volume":"103","author":"Younossi","year":"2019","journal-title":"Transplantation"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Li, T., Lin, X., Shen, B., Zhang, W., Liu, Y., Liu, H., Wang, Y., Zheng, L., and Zhi, F. (2022). Akkermansia Muciniphila Suppressing Nonalcoholic Steatohepatitis Associated Tumorigenesis through CXCR6+ Natural Killer T Cells. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1047570"},{"key":"ref_126","first-page":"E1306","article-title":"Probiotics Modulated Gut Microbiota Suppresses Hepatocellular Carcinoma Growth in Mice","volume":"113","author":"Li","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1016\/j.jhep.2023.07.005","article-title":"Bifidobacterium Pseudolongum-Generated Acetate Suppresses Non-Alcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma","volume":"79","author":"Song","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Lau, H.C.-H., Zhang, X., Ji, F., Lin, Y., Liang, W., Li, Q., Chen, D., Fong, W., Kang, X., and Liu, W. (2024). Lactobacillus Acidophilus Suppresses Non-Alcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma through Producing Valeric Acid. EBioMedicine, 100.","DOI":"10.1016\/j.ebiom.2023.104952"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1136\/gutjnl-2019-319664","article-title":"Dietary Cholesterol Drives Fatty Liver-Associated Liver Cancer by Modulating Gut Microbiota and Metabolites","volume":"70","author":"Zhang","year":"2021","journal-title":"Gut"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/s41571-018-0073-4","article-title":"Molecular Therapies and Precision Medicine for Hepatocellular Carcinoma","volume":"15","author":"Llovet","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1056\/NEJMoa1915745","article-title":"Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma","volume":"382","author":"Finn","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1200\/JCO.2022.40.4_suppl.379","article-title":"Phase 3 Randomized, Open-Label, Multicenter Study of Tremelimumab (T) and Durvalumab (D) as First-Line Therapy in Patients (Pts) with Unresectable Hepatocellular Carcinoma (uHCC): HIMALAYA","volume":"40","author":"Chan","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"3612","DOI":"10.1002\/cam4.4747","article-title":"Efficacy and Safety of PD-1 Inhibitor Combined with Antiangiogenic Therapy for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study","volume":"11","author":"Yao","year":"2022","journal-title":"Cancer Med."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1158\/2159-8290.CD-19-0074","article-title":"\u03b2-Catenin Activation Promotes Immune Escape and Resistance to Anti-PD-1 Therapy in Hepatocellular Carcinoma","volume":"9","author":"Bresnahan","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1158\/2159-8290.CD-16-0932","article-title":"Gut Microbiota Promotes Obesity-Associated Liver Cancer through PGE2-Mediated Suppression of Antitumor Immunity","volume":"7","author":"Loo","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1002\/hep.32447","article-title":"Emerging Immunotherapy for HCC: A Guide for Hepatologists","volume":"75","author":"Foerster","year":"2022","journal-title":"Hepatology"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1126\/science.aan3706","article-title":"Gut Microbiome Influences Efficacy of PD-1-Based Immunotherapy against Epithelial Tumors","volume":"359","author":"Routy","year":"2018","journal-title":"Science"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1007\/s12029-024-01095-7","article-title":"Concomitant Medications Alter Clinical Outcomes in Patients with Advanced Digestive Tract Cancer Receiving PD-1 Checkpoint Inhibitors Combined with Antiangiogenetic Agents","volume":"55","author":"Wang","year":"2024","journal-title":"J. Gastrointest. Cancer"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1159\/000518090","article-title":"Use of Antibiotics during Immune Checkpoint Inhibitor Treatment Is Associated with Lower Survival in Hepatocellular Carcinoma","volume":"10","author":"Cheung","year":"2021","journal-title":"Liver Cancer"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1159\/000519108","article-title":"Early Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma","volume":"10","author":"Fessas","year":"2021","journal-title":"Liver Cancer"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"100747","DOI":"10.1016\/j.jhepr.2023.100747","article-title":"Association between Antibiotics and Adverse Oncological Outcomes in Patients Receiving Targeted or Immune-Based Therapy for Hepatocellular Carcinoma","volume":"5","author":"Pinato","year":"2023","journal-title":"JHEP Rep. Innov. Hepatol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"e003334","DOI":"10.1136\/jitc-2021-003334","article-title":"Gut Microbiome Is Associated with the Clinical Response to Anti-PD-1 Based Immunotherapy in Hepatobiliary Cancers","volume":"9","author":"Mao","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"e004779","DOI":"10.1136\/jitc-2022-004779","article-title":"Gut Microbiota and Metabolites Associate with Outcomes of Immune Checkpoint Inhibitor-Treated Unresectable Hepatocellular Carcinoma","volume":"10","author":"Lee","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/s40425-019-0650-9","article-title":"Gut Microbiome Affects the Response to Anti-PD-1 Immunotherapy in Patients with Hepatocellular Carcinoma","volume":"7","author":"Zheng","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1002\/hep4.1905","article-title":"Gut Dysbiosis and Fecal Calprotectin Predict Response to Immune Checkpoint Inhibitors in Patients With Hepatocellular Carcinoma","volume":"6","author":"Ponziani","year":"2022","journal-title":"Hepatol. Commun."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"e008686","DOI":"10.1136\/jitc-2023-008686","article-title":"Characterizations of Multi-Kingdom Gut Microbiota in Immune Checkpoint Inhibitor-Treated Hepatocellular Carcinoma","volume":"12","author":"Zhu","year":"2024","journal-title":"J. Immunother. Cancer"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1002\/ijc.34118","article-title":"Dynamic Microbiome and Metabolome Analyses Reveal the Interaction between Gut Microbiota and Anti-PD-1 Based Immunotherapy in Hepatocellular Carcinoma","volume":"151","author":"Wu","year":"2022","journal-title":"Int. J. Cancer"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/jgh.15715","article-title":"Toward a Postbiotic Era of Microbiome Science: Opportunities to Advance Immunotherapies for Hepatocellular Carcinoma","volume":"37","author":"Nakatsu","year":"2022","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"e3639","DOI":"10.1002\/jgm.3639","article-title":"Akkermansia Muciniphila Might Improve Anti-PD-1 Therapy against HCC by Changing Host Bile Acid Metabolism","volume":"26","author":"Lan","year":"2024","journal-title":"J. Gene Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1038\/s41591-019-0559-3","article-title":"A Library of Human Gut Bacterial Isolates Paired with Longitudinal Multiomics Data Enables Mechanistic Microbiome Research","volume":"25","author":"Poyet","year":"2019","journal-title":"Nat. Med."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1016\/j.cell.2018.08.047","article-title":"Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT","volume":"174","author":"Suez","year":"2018","journal-title":"Cell"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/S2468-1253(23)00357-6","article-title":"Fine-Tuning the Gut Ecosystem: The Current Landscape and Outlook of Artificial Microbiome Therapeutics","volume":"9","author":"Porcari","year":"2024","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Wie\u00ebrs, G., Belkhir, L., Enaud, R., Leclercq, S., Philippart de Foy, J.-M., Dequenne, I., de Timary, P., and Cani, P.D. (2020). How Probiotics Affect the Microbiota. Front. Cell. Infect. Microbiol., 9.","DOI":"10.3389\/fcimb.2019.00454"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1736974","DOI":"10.1080\/19490976.2020.1736974","article-title":"Probiotic-Directed Modulation of Gut Microbiota Is Basal Microbiome Dependent","volume":"12","author":"Hou","year":"2020","journal-title":"Gut Microbes"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/2\/84\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:25:52Z","timestamp":1759919152000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/2\/84"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,9]]},"references-count":155,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["cells14020084"],"URL":"https:\/\/doi.org\/10.3390\/cells14020084","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,9]]}}}