肠道菌群及代谢物与乙肝相关肝病关系的研究进展
Research Progress on the Relationship between Gut Microbiota and Metabolites and Hepatitis B-Related Liver Disease
DOI: 10.12677/acm.2024.14112881, PDF,   
作者: 何 欢*, 兰英华#：重庆医科大学附属第二医院感染科，重庆
关键词: 肠道微生物；代谢物；肝脏；乙肝；肝硬化；肝癌；Gut Microbiota； Metabolites； Liver； Hepatitis B； Cirrhosis； Hepatocarcinoma
摘要: 全球乙型肝炎病毒感染者人数众多，如未进行及时、有效的治疗，慢性乙型肝炎往往会进展为肝硬化、肝细胞癌和肝衰竭等。越来越多的证据表明，肠道菌群及代谢物与慢性乙型肝炎病毒(HBV)感染相关肝病的疾病发展密切相关。粪菌移植和益生菌干预等方法可抑制乙肝相关肝病进展，在多种肝脏疾病的治疗中发挥着重要作用。本文就肠道菌群及代谢物与乙肝相关肝病关系的研究进展作一综述，为乙肝相关肝病的病理生理学机制、诊断和治疗提供新的见解。
Abstract: There are a large number of patients infected with hepatitis B virus in the world, and if there is no timely and effective treatment, chronic hepatitis B often progresses to liver cirrhosis, hepatocellular carcinoma and liver failure. Accumulating evidence suggests that gut microbiota and metabolites are closely associated with the development of chronic hepatitis B virus (HBV) infection-related liver disease. Methods such as fecal bacteria transplantation and probiotic intervention can inhibit the progression of hepatitis B-related liver disease and play an important role in the treatment of a variety of liver diseases. This article reviews the research progress on the relationship between gut microbiota and hepatitis B-related liver disease, and provides new insights into the pathophysiology, diagnosis and treatment of hepatitis B-related liver disease.
文章引用：何欢, 兰英华. 肠道菌群及代谢物与乙肝相关肝病关系的研究进展[J]. 临床医学进展, 2024, 14(11): 316-323. https://doi.org/10.12677/acm.2024.14112881

参考文献

[1] Hsu, Y., Huang, D.Q. and Nguyen, M.H. (2023) Global Burden of Hepatitis B Virus: Current Status, Missed Opportunities and a Call for Action. Nature Reviews Gastroenterology & Hepatology, 20, 524-537. [Google Scholar] [CrossRef] [PubMed]
[2] 尤红, 王福生, 李太生, 等. 慢性乙型肝炎防治指南(2022年版) [J]. 实用肝脏病杂志, 2023, 26(3): 457-478.
[3] Albillos, A., de Gottardi, A. and Rescigno, M. (2020) The Gut-Liver Axis in Liver Disease: Pathophysiological Basis for Therapy. Journal of Hepatology, 72, 558-577. [Google Scholar] [CrossRef] [PubMed]
[4] Wang, X., Chen, L., Wang, H., Cai, W. and Xie, Q. (2020) Modulation of Bile Acid Profile by Gut Microbiota in Chronic Hepatitis B. Journal of Cellular and Molecular Medicine, 24, 2573-2581. [Google Scholar] [CrossRef] [PubMed]
[5] Chen, Y., Yang, F., Lu, H., Wang, B., Chen, Y., Lei, D., et al. (2011) Characterization of Fecal Microbial Communities in Patients with Liver Cirrhosis. Hepatology, 54, 562-572. [Google Scholar] [CrossRef] [PubMed]
[6] Zhu, Q., Xia, P., Zhou, X., Li, X., Guo, W., Zhu, B., et al. (2019) Hepatitis B Virus Infection Alters Gut Microbiota Composition in Mice. Frontiers in Cellular and Infection Microbiology, 9, Article 377. [Google Scholar] [CrossRef] [PubMed]
[7] Li, X., Wu, S., Du, Y., Yang, L., Li, Y. and Hong, B. (2020) Entecavir Therapy Reverses Gut Microbiota Dysbiosis Induced by Hepatitis B Virus Infection in a Mouse Model. International Journal of Antimicrobial Agents, 56, Article 106000. [Google Scholar] [CrossRef] [PubMed]
[8] Lu, Y., He, C., Wang, Y., Ai, Z., Liang, P. and Yang, C. (2020) Effect of Entecavir on the Intestinal Microflora in Patients with Chronic Hepatitis B: A Controlled Cross-Sectional and Longitudinal Real-World Study. Infectious Diseases and Therapy, 10, 241-252. [Google Scholar] [CrossRef] [PubMed]
[9] Long, J., Gong, J., Zhu, H., Liu, X., Li, L., Chen, B., et al. (2023) Difference of Gut Microbiota between Patients with Negative and Positive HBeAg in Chronic Hepatitis B and the Effect of Tenofovir Alafenamide on Intestinal Flora. Frontiers in Microbiology, 14, Article 1232180. [Google Scholar] [CrossRef] [PubMed]
[10] Shen, Y., Wu, S., Chen, Y., Li, X., Zhu, Q., Nakayama, K., et al. (2022) Alterations in Gut Microbiome and Metabolomics in Chronic Hepatitis B Infection-Associated Liver Disease and Their Impact on Peripheral Immune Response. Gut Microbes, 15, Article 2155018. [Google Scholar] [CrossRef] [PubMed]
[11] Joo, E., Cheong, H.S., Kwon, M., Sohn, W., Kim, H. and Cho, Y.K. (2021) Relationship between Gut Microbiome Diversity and Hepatitis B Viral Load in Patients with Chronic Hepatitis B. Gut Pathogens, 13, Article No. 65. [Google Scholar] [CrossRef] [PubMed]
[12] Gola, A., Dorrington, M.G., Speranza, E., Sala, C., Shih, R.M., Radtke, A.J., et al. (2020) Commensal-Driven Immune Zonation of the Liver Promotes Host Defence. Nature, 589, 131-136. [Google Scholar] [CrossRef] [PubMed]
[13] Shu, W., Shanjian, C., Jinpiao, L. and Qishui, O. (2022) Gut Microbiota Dysbiosis in Patients with Hepatitis B Virus-Related Cirrhosis. Annals of Hepatology, 27, Article 100676. [Google Scholar] [CrossRef] [PubMed]
[14] Sharma, S.P., Gupta, H., Kwon, G., Lee, S.Y., Song, S.H., Kim, J.S., et al. (2024) Gut Microbiome and Metabolome Signatures in Liver Cirrhosis-Related Complications. Clinical and Molecular Hepatology, 30, 845-862. [Google Scholar] [CrossRef] [PubMed]
[15] Chen, Z., Xie, Y., Zhou, F., Zhang, B., Wu, J., Yang, L., et al. (2020) Featured Gut Microbiomes Associated with the Progression of Chronic Hepatitis B Disease. Frontiers in Microbiology, 11, Article 383. [Google Scholar] [CrossRef] [PubMed]
[16] Greten, T.F., Abou-Alfa, G.K., Cheng, A.L., et al. (2021) Society for Immunotherapy of Cancer (SITC) Clinical Practice Guideline on Immunotherapy for the Treatment of Hepatocellular Carcinoma. The Journal for ImmunoTherapy of Cancer, 9, e002794.
[17] Llovet, J.M., Kelley, R.K., Villanueva, A., Singal, A.G., Pikarsky, E., Roayaie, S., et al. (2021) Hepatocellular Carcinoma. Nature Reviews Disease Primers, 7, Article No. 6. [Google Scholar] [CrossRef] [PubMed]
[18] Zhang, C., Liu, S. and Yang, M. (2021) Hepatocellular Carcinoma and Obesity, Type 2 Diabetes Mellitus, Cardiovascular Disease: Causing Factors, Molecular Links, and Treatment Options. Frontiers in Endocrinology, 12, Article 808526. [Google Scholar] [CrossRef] [PubMed]
[19] Ponziani, F.R., Bhoori, S., Castelli, C., Putignani, L., Rivoltini, L., Del Chierico, F., et al. (2019) Hepatocellular Carcinoma Is Associated with Gut Microbiota Profile and Inflammation in Nonalcoholic Fatty Liver Disease. Hepatology, 69, 107-120. [Google Scholar] [CrossRef] [PubMed]
[20] Yu, L. and Schwabe, R.F. (2017) The Gut Microbiome and Liver Cancer: Mechanisms and Clinical Translation. Nature Reviews Gastroenterology & Hepatology, 14, 527-539. [Google Scholar] [CrossRef] [PubMed]
[21] Liu, Q., Li, F., Zhuang, Y., Xu, J., Wang, J., Mao, X., et al. (2019) Alteration in Gut Microbiota Associated with Hepatitis B and Non-Hepatitis Virus Related Hepatocellular Carcinoma. Gut Pathogens, 11, Article No. 1. [Google Scholar] [CrossRef] [PubMed]
[22] Liu, B., Zhou, Z., Jin, Y., Lu, J., Feng, D., Peng, R., et al. (2022) Hepatic Stellate Cell Activation and Senescence Induced by Intrahepatic Microbiota Disturbances Drive Progression of Liver Cirrhosis toward Hepatocellular Carcinoma. Journal for ImmunoTherapy of Cancer, 10, e003069. [Google Scholar] [CrossRef] [PubMed]
[23] Qu, D., Wang, Y., Xia, Q., Chang, J., Jiang, X. and Zhang, H. (2022) Intratumoral Microbiome of Human Primary Liver Cancer. Hepatology Communications, 6, 1741-1752. [Google Scholar] [CrossRef] [PubMed]
[24] Xiang, Z., Li, J., Lu, D., Wei, X. and Xu, X. (2022) Advances in Multi-Omics Research on Viral Hepatitis. Frontiers in Microbiology, 13, Article 987324. [Google Scholar] [CrossRef] [PubMed]
[25] Oliphant, K. and Allen-Vercoe, E. (2019) Macronutrient Metabolism by the Human Gut Microbiome: Major Fermentation By-Products and Their Impact on Host Health. Microbiome, 7, Article No. 91. [Google Scholar] [CrossRef] [PubMed]
[26] Schulthess, J., Pandey, S., Capitani, M., Rue-Albrecht, K.C., Arnold, I., Franchini, F., et al. (2019) The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages. Immunity, 50, 432-445.e7. [Google Scholar] [CrossRef] [PubMed]
[27] Zeng, Y., Chen, S., Fu, Y., Wu, W., Chen, T., Chen, J., et al. (2019) Gut Microbiota Dysbiosis in Patients with Hepatitis B Virus-Induced Chronic Liver Disease Covering Chronic Hepatitis, Liver Cirrhosis and Hepatocellular Carcinoma. Journal of Viral Hepatitis, 27, 143-155. [Google Scholar] [CrossRef] [PubMed]
[28] Ren, Z., Li, A., Jiang, J., Zhou, L., Yu, Z., Lu, H., et al. (2018) Gut Microbiome Analysis as a Tool towards Targeted Non-Invasive Biomarkers for Early Hepatocellular Carcinoma. Gut, 68, 1014-1023. [Google Scholar] [CrossRef] [PubMed]
[29] Sayin, S.I., Wahlström, A., Felin, J., Jäntti, S., Marschall, H., Bamberg, K., et al. (2013) Gut Microbiota Regulates Bile Acid Metabolism by Reducing the Levels of Tauro-Beta-Muricholic Acid, a Naturally Occurring FXR Antagonist. Cell Metabolism, 17, 225-235. [Google Scholar] [CrossRef] [PubMed]
[30] Jia, W., Xie, G. and Jia, W. (2017) Bile Acid-Microbiota Crosstalk in Gastrointestinal Inflammation and Carcinogenesis. Nature Reviews Gastroenterology & Hepatology, 15, 111-128. [Google Scholar] [CrossRef] [PubMed]
[31] Yan, H., Zhong, G., Xu, G., et al. (2012) Sodium Taurocholate Co-Transporting Polypeptide Is a Functional Receptor for Human Hepatitis B and D Virus. Elife, 1, e00049.
[32] König, A., Döring, B., Mohr, C., Geipel, A., Geyer, J. and Glebe, D. (2014) Kinetics of the Bile Acid Transporter and Hepatitis B Virus Receptor Na+/Taurocholate Co-Transporting Polypeptide (NTCP) in Hepatocytes. Journal of Hepatology, 61, 867-875. [Google Scholar] [CrossRef] [PubMed]
[33] Oehler, N., Volz, T., Bhadra, O.D., Kah, J., Allweiss, L., Giersch, K., et al. (2014) Binding of Hepatitis B Virus to Its Cellular Receptor Alters the Expression Profile of Genes of Bile Acid Metabolism. Hepatology, 60, 1483-1493. [Google Scholar] [CrossRef] [PubMed]
[34] Wang, X., Xie, G., Zhao, A., Zheng, X., Huang, F., Wang, Y., et al. (2016) Serum Bile Acids Are Associated with Pathological Progression of Hepatitis B-Induced Cirrhosis. Journal of Proteome Research, 15, 1126-1134. [Google Scholar] [CrossRef] [PubMed]
[35] Radreau, P., Porcherot, M., Ramiére, C., Mouzannar, K., Lotteau, V. and André, P. (2016) Reciprocal Regulation of Farnesoid X Receptor Α Activity and Hepatitis B Virus Replication in Differentiated HepaRG Cells and Primary Human Hepatocytes. The FASEB Journal, 30, 3146-3154. [Google Scholar] [CrossRef] [PubMed]
[36] Agus, A., Planchais, J. and Sokol, H. (2018) Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host & Microbe, 23, 716-724. [Google Scholar] [CrossRef] [PubMed]
[37] Mehraj, V. and Routy, J. (2015) Tryptophan Catabolism in Chronic Viral Infections: Handling Uninvited Guests. International Journal of Tryptophan Research, 8, 41-48. [Google Scholar] [CrossRef] [PubMed]
[38] Canyelles, M., Tondo, M., Cedó, L., Farràs, M., Escolà-Gil, J.C. and Blanco-Vaca, F. (2018) Trimethylamine N-Oxide: A Link among Diet, Gut Microbiota, Gene Regulation of Liver and Intestine Cholesterol Homeostasis and HDL Function. International Journal of Molecular Sciences, 19, Article 3228. [Google Scholar] [CrossRef] [PubMed]
[39] Chittim, C.L., Martínez del Campo, A. and Balskus, E.P. (2018) Gut Bacterial Phospholipase Ds Support Disease-Associated Metabolism by Generating Choline. Nature Microbiology, 4, 155-163. [Google Scholar] [CrossRef] [PubMed]
[40] Romano, K.A., Martinez-del Campo, A., Kasahara, K., Chittim, C.L., Vivas, E.I., Amador-Noguez, D., et al. (2017) Metabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption. Cell Host & Microbe, 22, 279-290.e7. [Google Scholar] [CrossRef] [PubMed]
[41] Cox, I.J., Aliev, A.E., Crossey, M.M., Dawood, M., Al-Mahtab, M., Akbar, S.M., et al. (2016) Urinary Nuclear Magnetic Resonance Spectroscopy of a Bangladeshi Cohort with Hepatitis-B Hepatocellular Carcinoma: A Biomarker Corroboration Study. World Journal of Gastroenterology, 22, 4191-4200. [Google Scholar] [CrossRef] [PubMed]
[42] Cantorna, M.T., Snyder, L. and Arora, J. (2019) Vitamin a and Vitamin D Regulate the Microbial Complexity, Barrier Function, and the Mucosal Immune Responses to Ensure Intestinal Homeostasis. Critical Reviews in Biochemistry and Molecular Biology, 54, 184-192. [Google Scholar] [CrossRef] [PubMed]
[43] Karl, J.P., Meydani, M., Barnett, J.B., Vanegas, S.M., Barger, K., Fu, X., et al. (2017) Fecal Concentrations of Bacterially Derived Vitamin K Forms Are Associated with Gut Microbiota Composition but Not Plasma or Fecal Cytokine Concentrations in Healthy Adults. The American Journal of Clinical Nutrition, 106, 1052-1061. [Google Scholar] [CrossRef] [PubMed]
[44] Koop, A.H., Mousa, O.Y., Pham, L.E., Corral-Hurtado, J.E., Pungpapong, S. and Keaveny, A.P. (2018) An Argument for Vitamin D, A, and Zinc Monitoring in Cirrhosis. Annals of Hepatology, 17, 920-932. [Google Scholar] [CrossRef] [PubMed]

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