Gut Microbiome Modulation in Hepatocellular Carcinoma: Preventive Role in NAFLD/NASH Progression and Potential Applications in Immunotherapy-Based Strategies
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% preval...
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2025-01-01
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| author | Elisa Monti Clara Vianello Ilaria Leoni Giuseppe Galvani Annalisa Lippolis Federica D’Amico Sara Roggiani Claudio Stefanelli Silvia Turroni Francesca Fornari |
| author_facet | Elisa Monti Clara Vianello Ilaria Leoni Giuseppe Galvani Annalisa Lippolis Federica D’Amico Sara Roggiani Claudio Stefanelli Silvia Turroni Francesca Fornari |
| author_sort | Elisa Monti |
| collection | DOAJ |
| description | 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–liver 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–liver axis holds promise for liver cancer prevention and treatment, especially if personalized options will be considered. |
| format | Article |
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| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-8aacbbe166fe4ad0a3948bffc65815582025-01-24T13:26:37ZengMDPI AGCells2073-44092025-01-011428410.3390/cells14020084Gut Microbiome Modulation in Hepatocellular Carcinoma: Preventive Role in NAFLD/NASH Progression and Potential Applications in Immunotherapy-Based StrategiesElisa Monti0Clara Vianello1Ilaria Leoni2Giuseppe Galvani3Annalisa Lippolis4Federica D’Amico5Sara Roggiani6Claudio Stefanelli7Silvia Turroni8Francesca Fornari9Department for Life Quality Studies, University of Bologna, Corso d’Augusto 237, 47921 Rimini, ItalyDepartment for Life Quality Studies, University of Bologna, Corso d’Augusto 237, 47921 Rimini, ItalyDepartment for Life Quality Studies, University of Bologna, Corso d’Augusto 237, 47921 Rimini, ItalyDepartment for Life Quality Studies, University of Bologna, Corso d’Augusto 237, 47921 Rimini, ItalyDepartment for Life Quality Studies, University of Bologna, Corso d’Augusto 237, 47921 Rimini, ItalyUnit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, ItalyUnit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, ItalyDepartment for Life Quality Studies, University of Bologna, Corso d’Augusto 237, 47921 Rimini, ItalyUnit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, ItalyDepartment for Life Quality Studies, University of Bologna, Corso d’Augusto 237, 47921 Rimini, ItalyHepatocellular 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–liver 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–liver axis holds promise for liver cancer prevention and treatment, especially if personalized options will be considered.https://www.mdpi.com/2073-4409/14/2/84HCCNAFLDmicrobiomeimmunotherapy |
| spellingShingle | Elisa Monti Clara Vianello Ilaria Leoni Giuseppe Galvani Annalisa Lippolis Federica D’Amico Sara Roggiani Claudio Stefanelli Silvia Turroni Francesca Fornari Gut Microbiome Modulation in Hepatocellular Carcinoma: Preventive Role in NAFLD/NASH Progression and Potential Applications in Immunotherapy-Based Strategies Cells HCC NAFLD microbiome immunotherapy |
| title | Gut Microbiome Modulation in Hepatocellular Carcinoma: Preventive Role in NAFLD/NASH Progression and Potential Applications in Immunotherapy-Based Strategies |
| title_full | Gut Microbiome Modulation in Hepatocellular Carcinoma: Preventive Role in NAFLD/NASH Progression and Potential Applications in Immunotherapy-Based Strategies |
| title_fullStr | Gut Microbiome Modulation in Hepatocellular Carcinoma: Preventive Role in NAFLD/NASH Progression and Potential Applications in Immunotherapy-Based Strategies |
| title_full_unstemmed | Gut Microbiome Modulation in Hepatocellular Carcinoma: Preventive Role in NAFLD/NASH Progression and Potential Applications in Immunotherapy-Based Strategies |
| title_short | Gut Microbiome Modulation in Hepatocellular Carcinoma: Preventive Role in NAFLD/NASH Progression and Potential Applications in Immunotherapy-Based Strategies |
| title_sort | gut microbiome modulation in hepatocellular carcinoma preventive role in nafld nash progression and potential applications in immunotherapy based strategies |
| topic | HCC NAFLD microbiome immunotherapy |
| url | https://www.mdpi.com/2073-4409/14/2/84 |
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