肠道菌群与肝脏相关疾病的研究进展
Research Progress of Intestinal Flora and Liver Related Diseases
摘要: 肠道微生物群的组成与非酒精性脂肪肝病(Nonalcoholic fatty liver disease, NAFLD)、酒精性肝病(Alcoholic liver disease, ALD)、病毒性肝炎、自身免疫性肝病(autoimmune liver disease, AILD)、肝细胞癌(hepatocellular carcinoma, HCC)等多种慢性肝病的发病机制密切相关。本文旨在通过论述肠道菌群与肝脏相关疾病之间的相互关系,以期为肝脏相关疾病的临床研究提供更多理论依据,以期作为治疗肝脏相关疾病的新方向。
Abstract: The composition of intestinal microbiota is closely related to the pathogenesis of nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), viral hepatitis, autoimmune liver disease,AILD, hepatocellular carcinoma (HCC) and other chronic liver diseases. This paper aims to discuss the relationship between intestinal flora and liver related diseases, in order to provide more theoretical basis for clinical research of liver related diseases, and as a new direction for the treatment of liver related diseases.
文章引用:李惠, 马臻棋, 王学红, 马文霞, 杨丽萍. 肠道菌群与肝脏相关疾病的研究进展[J]. 临床医学进展, 2021, 11(7): 3185-3190. https://doi.org/10.12677/ACM.2021.117462

参考文献

[1] Milosevic, I., Vujovic, A., Barac, A., Djelic, M., Korac, M., Radovanovic Spurnic, A., Gmizic, I., Stevanovic, O., Djordjevic, V., Lekic, N., Russo, E. and Amedei, A. (2019) Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature. International Journal of Molecular Sciences, 20, 395. [Google Scholar] [CrossRef] [PubMed]
[2] Lozupone, C.A., Stombaugh, J.I., Gordon, J.I., Jansson, J.K. and Knight, R. (2012) Diversity, Stability and Resilience of the Human Gut Microbiota. Nature, 489, 220-230. [Google Scholar] [CrossRef] [PubMed]
[3] Tremaroli, V. and Bäckhed, F. (2012) Functional Interactions between the Gut Microbiota and Host Metabolism. Nature, 489, 242-249. [Google Scholar] [CrossRef] [PubMed]
[4] 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]
[5] Cassard, A.M. and Ciocan, D. (2017) Microbiota, a Key Player in Alcoholic Liver Disease. Clinical and Molecular Hepatology, 24, 100-107. [Google Scholar] [CrossRef] [PubMed]
[6] Hartmann, P., Seebauer, C.T. and Schnabl, B. (2015) Alcoholic Liver Disease: The Gut Microbiome and Liver Cross Talk. Alcoholism: Clinical and Experimental Research, 39, 763-775. [Google Scholar] [CrossRef] [PubMed]
[7] Szabo, G. (2014) Gut-Liver Axis in Alcoholic Liver Disease. Gastroenterology, 148, 30-36. [Google Scholar] [CrossRef] [PubMed]
[8] Xie, G., Zhong, W., Zheng, X., Li, Q., Qiu, Y., Li, H., Chen, H., Zhou, Z. and Jia, W. (2013) Chronic Ethanol Consumption Alters Mammalian Gastrointestinal Content Metabolites. Journal of Proteome Research, 12, 3297-3306. [Google Scholar] [CrossRef] [PubMed]
[9] Macnaughtan, J. and Jalan, R. (2015) Clinical and Pathophysiological Consequences of Alterations in the Microbiome in Cirrhosis. The American Journal of Gastroenterology, 110, 1399-1410. [Google Scholar] [CrossRef] [PubMed]
[10] Leclercq, S., Matamoros, S., Cani, P.D., et al. (2014) Intestinal Permeability, Gut-Bacterial Dysbiosis, and Behavioral Markers of Alcohol-Dependence Severity. Proceedings of the National Academy of Sciences of the United States of America, 111, E4485-E4493. [Google Scholar] [CrossRef] [PubMed]
[11] Pradere, J.P., Troeger, J.S., Dapito, D.H., Mencin, A.A. and Schwabe, R.F. (2010) Toll-Like Receptor 4 and Hepatic Fibrogenesis. Seminars in Liver Disease, 30, 232-244. [Google Scholar] [CrossRef] [PubMed]
[12] Chen, P., et al. (2015) Supplementation of Saturated Long-Chain Fatty Acids Maintains Intestinal Eubiosis and Reduces Ethanol-Induced Liver Injury in Mice. Gastroenterology, 148, 203-214.e216. [Google Scholar] [CrossRef] [PubMed]
[13] Llopis, M., Cassard, A.M., Wrzosek, L., et al. (2016) Intestinal Microbiota Contributes to Individual Susceptibility to Alcoholic Liver Disease. Gut, 65, 830-839. [Google Scholar] [CrossRef] [PubMed]
[14] Younossi, Z.M., Marchesini, G., Pinto-Cortez, H. and Petta, S. (2018) Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: Implications for Liver Transplantation. Transplantation, 2018, Article ID: 30335697. [Google Scholar] [CrossRef] [PubMed]
[15] 中华医学会肝病学分会脂肪肝和酒精性肝病学组. 非酒精性脂肪性肝病诊疗指南(2010年修订版) [J]. 胃肠病学和肝病学杂志, 2010, 19(6): 483-487.
[16] 非酒精性脂肪性肝病防治指南(2018更新版) [J]. 传染病信息, 2018, 31(5): 393-402+420.
[17] Michelotti, G.A., Machado, M.V. and Diehl, A.M. (2013) NAFLD, NASH and Liver Cancer. Nature Reviews Gastroenterology Hepatology, 10, 656-665. [Google Scholar] [CrossRef] [PubMed]
[18] Buzzetti, E., Pinzani, M. and Tsochatzis, E.A. (2016) The Multiple-Hit Pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD). Metabolism, 65, 1038-1048. [Google Scholar] [CrossRef] [PubMed]
[19] 柳惠未, 叶桦. 肠道菌群在非酒精性脂肪性肝病发病机制中的作用[J]. 中国现代医生, 2019, 57(6): 163-168.
[20] 廉晓晓, 郭晓霞. 肠-肝轴学说的研究进展[J]. 中西医结合肝病杂志, 2017, 27(4): 251-254.
[21] Le Roy, T., Llopis, M., Lepage, P., et al. (2013) Intestinal Microbiota Determines Development of Non-Alcoholic Fatty Liver Disease in Mice. Gut, 62, 1787-1794. [Google Scholar] [CrossRef] [PubMed]
[22] World Health Organization (2017) Global Hepatitis Report 2017. Geneva.
https://www.who.int/hepatitis/publications/global-hepatitis-report2017/en
[23] World Health Organization (2016) Global Health Sector Strategy on Viral Hepatitis, 2016-2021. Geneva. http://apps.who.int/iris/bitstream/10665/246177/1/WHO-HIV-2016.06-eng.pdf?ua51
[24] Aly, A.M., Adel, A., El-Gendy, A.O., Essam, T.M. and Aziz, R.K. (2016) Gut Microbiome Alterations in Patients with Stage 4 Hepatitis C. Gut Pathogens, 8, 42. [Google Scholar] [CrossRef] [PubMed]
[25] Heidrich, B., Vital, M., Plumeier, I., et al. (2018) Intestinal Microbiota in Patients with Chronic Hepatitis C with and without Cirrhosis Compared with Healthy Controls. Liver International, 38, 50-58. [Google Scholar] [CrossRef] [PubMed]
[26] Inoue, T., Nakayama, J., Moriya, K., Kawaratani, H., Momoda, R., Ito, K., Iio, E., Nojiri, S., Fujiwara, K., Yoneda, M., Yoshiji, H. and Tanaka, Y. (2018) Gut Dysbiosis Associated with Hepatitis C Virus Infection. Clinical Infectious Diseases, 67, 869-877. [Google Scholar] [CrossRef] [PubMed]
[27] 王睿, 王绮夏, 马雄. 肠道微生态与自身免疫性肝病[J]. 实用肝脏病杂志, 2020, 23(6): 773-776.
[28] Abe, K., Fujita, M., Hayashi, M., Okai, K., Takahashi, A. and Ohira, H. (2020) Gut and Oral Microbiota in Autoimmune Liver Disease. Fukushima Journal of Medical Science, 65, 71-75. [Google Scholar] [CrossRef] [PubMed]
[29] Lin, R., Zhou, L., Zhang, J. and Wang, B. (2015) Abnormal Intestinal Permeability and Microbiota in Patients with Autoimmune Hepatitis. International Journal of Clinical and Experimental Pathology, 8, 5153-5160.
[30] Wei, Y., Li, Y., Yan, L., Sun, C., Miao, Q., Wang, Q., Xiao, X., Lian, M., Li, B., Chen, Y., Zhang, J., Li, Y., Huang, B., Li, Y., Cao, Q., Fan, Z., Chen, X., Fang, J.Y., Gershwin, M.E., Tang, R. and Ma, X. (2019) Alterations of Gut Microbiome in Autoimmune Hepatitis. Gut, 69, 569-577. [Google Scholar] [CrossRef] [PubMed]
[31] Abe, K., Takahashi, A., Fujita, M., Imaizumi, H., Hayashi, M., Okai, K., et al. (2018) Dysbiosis of Oral Microbiota and Its Association with Salivary Immunological Biomarkers in Autoimmune Liver Disease. PLoS ONE, 13, e0198757. [Google Scholar] [CrossRef] [PubMed]
[32] Kaplan, M.M. and Gershwin, M.E. (2005) Primary Biliary Cirrhosis. The New England Journal of Medicine, 353, 1261-1273. [Google Scholar] [CrossRef
[33] Selmi, C., Bowlus, C.L., Gershwin, M.E. and Coppel, R.L. (2011) Primary Biliary Cirrhosis. The Lancet, 377, 1600-1609. [Google Scholar] [CrossRef
[34] Yu, L.X. 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]
[35] Gupta, H., Youn, G.S., Shin, M.J. and Suk, K.T. (2019) Role of Gut Microbiota in Hepatocarcinogenesis. Microorganisms, 7, 121. [Google Scholar] [CrossRef
[36] Ren, Z., Li, A., Jiang, J., Zhou, L., Yu, Z., Lu, H., Xie, H., Chen, X., Shao, L., Zhang, R., Xu, S., Zhang, H., Cui, G., Chen, X., Sun, R., Wen, H., Lerut, J.P., Kan, Q., Li, L. and Zheng, S. (2019) Gut Microbiome Analysis as a Tool towards Targeted Non-Invasive Biomarkers for Early Hepatocellular Carcinoma. Gut, 68, 1014-1023. [Google Scholar] [CrossRef] [PubMed]
[37] Wan, M.L.Y. and El-Nezami, H. (2018) Targeting Gut Microbiota in Hepatocellular Carcinoma: Probiotics as a Novel Therapy. Hepatobiliary Surgery, 7, 11-20. [Google Scholar] [CrossRef] [PubMed]
[38] Grat, M., Wronka, K.M., Krasnodebski, M., Masior, L., Lewandowski, Z., Kosinska, I., Grat, K., Stypulkowski, J., Rejowski, S., Wasilewicz, M., Galecka, M., Szachta, P. and Krawczyk, M. (2016) Profile of Gut Microbiota Associated with the Presence of Hepatocellular Cancer in Patients with Liver Cirrhosis. Transplantation Proceedings, 48, 1687-1691. [Google Scholar] [CrossRef] [PubMed]
[39] Louis, P. and Flint, H.J. (2009) Diversity, Metabolism and Microbial Ecology of Butyrate-Producing Bacteria from the Human Large Intestine. FEMS Microbiology Letters, 294, 1-8. [Google Scholar] [CrossRef] [PubMed]