肠-肝轴与酒精性肝病研究进展

摘要/Abstract

摘要： 酒精性肝病(ALD)是一种长期大量饮酒导致的慢性肝脏疾病,其发生、发展不仅与酒精代谢引发的氧应激和肝脏炎症相关,更与酗酒所致的肠道菌群紊乱密切相关。酒精通过干扰肠-肝轴促进ALD进展,其核心发病机制包括肠道屏障功能障碍、肠道菌群失调、细菌及其代谢产物(如脂多糖)经门静脉易位至肝脏,从而触发持续的炎症免疫反应导致肝损伤。深入理解肠道菌群在ALD中的作用可为ALD的防治提供新策略。本文旨在综述肠-肝轴在ALD中的相关作用机制及靶向肠-肝轴的治疗进展。

王伊歌, 杨松. 肠-肝轴与酒精性肝病研究进展[J]. 肝脏, 2026, 31(1): 7-11.

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参考文献

[1] Simon L, Souza-Smith F M, Molina P E. Alcohol-associated tissue injury: current views on pathophysiological mechanisms [J]. Annu Rev Physiol, 2022, 84(1): 87-112.
[2] Yan C, Hu W, Tu J, et al. Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease [J].J Transl Med, 2023, 21(1):300.
[3] Cheng Z, Yang L, Chu H. The role of gut microbiota, exosomes, and their interaction in the pathogenesis of ALD [J]. J Adv Res, 2025, 72: 353-367.
[4] Wu X, Fan X, Miyata T, et al. Recent advances in understanding of pathogenesis of alcohol-associated liver disease [J]. Annu Rev Pathol, 2023, 18:411-438.
[5] Pohl K, Moodley P, Dhanda A D. Alcohol′s impact on the gut and liver [J]. Nutrients, 2021, 13(9):3170.
[6] Zhu L, Wang Y, Pan C Q, et al. Gut microbiota in alcohol-related liver disease: pathophysiology and gut-brain cross talk [J]. Front Pharmacol. 2023, 14:1258062.
[7] Raya Tonetti F, Eguileor A, Mrdjen M, et al. Gut-liver axis: recent concepts in pathophysiology in alcohol-associated liver disease [J]. Hepatology, 2024, 80(6): 1342-1371.
[8] Sosnowski K, Przybylkowski A. Ethanol-induced changes to the gut microbiome compromise the intestinal homeostasis: a review [J]. Gut Microbes, 2024, 16(1): 2393272.
[9] Hyun J Y, Kim S K, Yoon S J, et al. Microbiome-based metabolic therapeutic approaches in alcoholic liver disease [J]. Int J Mol Sci, 2022, 23(15):8749.
[10] Goyal H, Fatima K, Kaur J. Understanding crosstalk between the gut and liver microbiome: pathogenesis to therapeutic approaches in liver cancer [J]. Cancer Cell Int, 2025, 25(1): 291.
[11] 吕威志, 刘辉, 乔艺.肠道菌群在酒精性肝病中的作用机制研究进展[J]. 微生物学报, 2025, 65 (10): 4295-4307.
[12] Kirundi J, Moghadamrad S, Urbaniak C. Microbiome-liver crosstalk: a multihit therapeutic target for liver disease [J]. World J Gastroenterol, 2023, 29(11): 1651-1668.
[13] Eom J A, Jeong J J, Han S H, et al. Gut-microbiota prompt activation of natural killer cell on alcoholic liver disease [J]. Gut Microbes, 2023, 15(2): 2281014.
[14] Hsu C L, Schnabl B. The gut-liver axis and gut microbiota in health and liver disease [J]. Nat Rev Microbiol, 2023, 21(11): 719-733.
[15] Chen L, Zhu Y, Hou X, et al. The role of gut bacteria and fungi in alcohol-associated liver disease [J]. Front Med (Lausanne), 2022, 9: 840752.
[16] Jew M H, Hsu C L. Alcohol, the gut microbiome, and liver disease [J]. J Gastroenterol Hepatol, 2023, 38(8): 1205-1210.
[17] Chung B S, Yang K, Park C, et al. Prolonged intestinal ethanol absorption and oxidative stress: revisiting the gut-liver axis in alcohol-associated disease [J]. Int J Mol Sci, 2025, 26(12):5442.
[18] Hsu C L, Wang Y, Duan Y, et al. Differences in bacterial translocation and liver injury in ethanol versus diet-induced liver disease [J]. Dig Dis Sci, 2023, 68(7): 3059-3069.
[19] Di Vincenzo F, Del Gaudio A, Petito V, et al. Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review [J]. Intern Emerg Med, 2024, 19(2):275-293.
[20] Liu J, Yang D, Wang X, et al. Gut microbiota targeted approach in the management of chronic liver diseases [J]. Front Cell Infect Microbiol, 2022, 12:774335.
[21] Mrdjen M, Huang E, Pathak V, et al. Dysregulated meta-organismal metabolism of aromatic amino acids in alcohol-associated liver disease [J]. Hepatol Commun, 2023, 7(11):e0284.
[22] Qian M, Liu J, Zhao D, et al. Aryl hydrocarbon receptor deficiency in intestinal epithelial cells aggravates alcohol-related liver disease [J]. Cell Mol Gastroenterol Hepatol, 2022, 13(1):233-256.
[23] Tripathi A, Debelius J, Brenner D A, et al. The gut-liver axis and the intersection with the microbiome [J]. Nat Rev Gastroenterol Hepatol, 2018, 15(7): 397-411.
[24] Zhang Y L, Li Z J, Gou H Z, et al. The gut microbiota-bile acid axis: A potential therapeutic target for liver fibrosis [J]. Front Cell Infect Microbiol, 2022, 12:945368.
[25] Lin X, Xia L, Zhou Y, et al. Crosstalk between bile acids and intestinal epithelium: multidimensional roles of farnesoid X receptor and takeda G protein receptor 5 [J]. Int J Mol Sci, 2025, 26(9):4240.
[26] Kuo C H, El-Omar E, Kao C Y, et al. Compositional and metabolomic shifts of the gut microbiome in alcohol-related liver disease [J]. J Gastroenterol Hepatol, 2025, 40(9): 2176-2189.
[27] Morel C, Chowdhary V, Thevkar Nagesh P, et al. Altered ethanol metabolism and increased oxidative stress enhance alcohol-associated liver injury in farnesoid X receptor-deficient mice [J]. Liver Int, 2023, 43(1): 100-114.
[28] Maccioni L, Leclercq I A, Schnabl B, et al.Host factors in dysregulation of the gut barrier function during alcohol-associated liver disease [J]. Int J Mol Sci, 2021, 22(23):12687.
[29] Chopyk D M, Grakoui A. Contribution of the intestinal microbiome and gut barrier to hepatic disorders [J]. Gastroenterology, 2020, 159(3): 849-863.
[30] Dukic M, Radonjic T, Jovanovic I, et al. Alcohol, inflammation, and microbiota in alcoholic liver disease [J]. Int J Mol Sci, 2023, 24(4):3735.
[31] Li H, Cheng S, Huo J, et al. Lactobacillus plantarum J26 alleviating alcohol-induced liver inflammation by maintaining the intestinal barrier and regulating MAPK signaling pathways [J]. Nutrients, 2022, 15(1):190.
[32] Shen H, Zhou L, Zhang H, et al. Dietary fiber alleviates alcoholic liver injury via Bacteroides acidifaciens and subsequent ammonia detoxification [J]. Cell Host Microbe, 2024, 32(8): 1331-1346.e6.
[33] Hou S, Yu J, Li Y, et al. Advances in fecal microbiota transplantation for gut dysbiosis-related diseases [J]. Adv Sci (Weinh), 2025, 12(13): e2413197.
[34] 赵彩霞,杨松.粪菌移植治疗重症酒精性肝炎研究进展[J].实用肝脏病杂志,2025,28(1):9-12.
[35] Pande A, Sharma S, Khillan V, et al. Fecal microbiota transplantation compared with prednisolone in severe alcoholic hepatitis patients: a randomized trial [J]. Hepatology International, 2023, 17(1): 249-261.
[36] Chen L, Hou X, Chu H. The novel role of phage particles in chronic liver diseases [J]. Microorganisms, 2023, 11(5):1181.
[37] Duan Y, Llorente C, Lang S, et al. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease [J]. Nature, 2019, 575(7783): 505-511.
[38] 刘海霞,樊卫平,周祥,等.肠道菌群在酒精性肝病中的作用及机制研究进展[J].检验医学与临床,2024,21(21):3256-3260.
[39] 王晓婷,曹翠,刘军锋,等.基于肠道菌群代谢探讨黄精多糖对酒精性肝病小鼠的保护作用[J].中草药,2025,56(16):5814-5825.