中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 41 Issue 12
Dec.  2025
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2025  >  41(12): 2629-2635

Latest research advances in intestinal flora-based targeted therapy for autoimmune liver disease

DOI: 10.12449/JCH251226
  • 1.

    The First Clinical Medical College of Gansu University of Chinese Medicine，Lanzhou 730000，China

  • 2.

    Department of Gastroenterology，The 940 Hospital of Joint Logistic Support Force of PLA，Lanzhou 730000，China

  • 3.

    Medical Service Training Center，The 940 Hospital of Joint Logistic Support Force of PLA，Lanzhou 730000，China

Research funding:

Project of Gansu Provincial Health Care Commission (GSWSKY2023-34);

Lanzhou Youth Science and Technology Talent Innovation Project (2024-QN-39)

More Information
  • Corresponding author: ZHAO Yong， 19692441@qq.com（ORCID： 0009-0000-6803-247X）; ZHANG Jiucong， zhangjiucong@163.com （ORCID： 0000-0003-4006-3033）
  • Received Date: 2025-04-24
  • Accepted Date: 2025-05-26
  • Published Date: 2025-12-25
    Abstract
  • The pathogenesis of autoimmune liver disease （AILD） remains unclear， leading to significant individual differences in clinical outcomes. Recent studies have shown that intestinal flora and its metabolites are closely associated with the development， progression， and pathogenesis of AILD through the gut-liver axis， and targeted therapy based on intestinal flora has provided new strategies for the treatment of AILD. This article systematically reviews the potential pathogenic mechanism of intestinal flora in AILD and the latest research advances in targeted therapeutic strategies and explores the possibility of targeted regulation of intestinal microecology to achieve treatment by analyzing the molecular mechanisms of immune disorders mediated by imbalance of intestinal flora， in order to provide a theoretical basis for clinical diagnosis and treatment.

     

    • FullText(HTML)
  • loading
    • References(50)
  • [1]
    QIU ZX, HUANG LX, WANG XX, et al. Exploring the pathogenesis of autoimmune liver diseases from the heterogeneity of target cells[J]. J Clin Transl Hepatol, 2024, 12( 7): 659- 666. DOI: 10.14218/JCTH.2023.00531.
    [2]
    ZHAO YJ, XIE L, ZHANG YT, et al. Pyroptosis: A new bridge connecting gut microbiota and liver diseases[J]. J Clin Hepatol, 2024, 40( 9): 1908- 1915. DOI: 10.12449/JCH240930.

    赵奕杰, 谢露, 张亚亭, 等. 细胞焦亡: 连接肠道菌群与肝脏疾病的新桥梁[J]. 临床肝胆病杂志, 2024, 40( 9): 1908- 1915. DOI: 10.12449/JCH240930.
    [3]
    LI R, MAO ZS, YE XJ, et al. Human gut microbiome and liver diseases: From correlation to causation[J]. Microorganisms, 2021, 9( 5): 1017. DOI: 10.3390/microorganisms9051017.
    [4]
    CHENG ZL, YANG L, CHU HK. The gut microbiota: A novel player in autoimmune hepatitis[J]. Front Cell Infect Microbiol, 2022, 12: 947382. DOI: 10.3389/fcimb.2022.947382.
    [5]
    BERINGER A, MIOSSEC P. IL-17 and IL-17-producing cells and liver diseases, with focus on autoimmune liver diseases[J]. Autoimmun Rev, 2018, 17( 12): 1176- 1185. DOI: 10.1016/j.autrev.2018.06.008.
    [6]
    YANG Y, CHOI J, CHEN Y, et al. E. coli and the etiology of human PBC: Antimitochondrial antibodies and spreading determinants[J]. Hepatology, 2022, 75( 2): 266- 279. DOI: 10.1002/hep.32172.
    [7]
    TERJUNG B, SPENGLER U. Atypical p-ANCA in PSC and AIH: A Hint Toward a“leaky gut”[J]. Clin Rev Allergy Immunol, 2009, 36( 1): 40- 51. DOI: 10.1007/s12016-008-8088-8.
    [8]
    GOEL R, EAPEN CE. Recognizing dysfunctional innate and adaptive immune responses contributing to liver damage in patients with cirrhosis[J]. J Clin Exp Hepatol, 2022, 12( 3): 993- 1002. DOI: 10.1016/j.jceh.2021.10.001.
    [9]
    LIU H, ZHAO J, ZHANG WJ, et al. Impacts of sodium butyrate on intestinal mucosal barrier and intestinal microbial community in a weaned piglet model[J]. Front Microbiol, 2022, 13: 1041885. DOI: 10.3389/fmicb.2022.1041885.
    [10]
    KAYAMA H, OKUMURA R, TAKEDA K. Interaction between the microbiota, epithelia, and immune cells in the intestine[J]. Annu Rev Immunol, 2020, 38: 23- 48. DOI: 10.1146/annurev-immunol-070119-115104.
    [11]
    INAMINE T, SCHNABL B. Immunoglobulin A and liver diseases[J]. J Gastroenterol, 2018, 53( 6): 691- 700. DOI: 10.1007/s00535-017-1400-8.
    [12]
    LAPIDOT Y, AMIR A, BEN-SIMON S, et al. Alterations of the salivary and fecal microbiome in patients with primary sclerosing cholangitis[J]. Hepatol Int, 2021, 15( 1): 191- 201. DOI: 10.1007/s12072-020-10089-z.
    [13]
    ÖZDIRIK B, SCHERF M, BRUMERCEK A, et al. Biliary microbial patterns in primary sclerosing cholangitis are linked to poorer transplant-free survival[J]. Hepatol Commun, 2023, 7( 6): e0156. DOI: 10.1097/HC9.000-0000000000156.
    [14]
    BABU G, MOHANTY B. Neurotensin modulation of lipopolysaccharide induced inflammation of gut-liver axis: Evaluation using neurotensin receptor agonist and antagonist[J]. Neuropeptides, 2023, 97: 102297. DOI: 10.1016/j.npep.2022.102297.
    [15]
    VERMA S, REDDY P, SOWDHAMINI R. Integrated approaches for the recognition of small molecule inhibitors for Toll-like receptor 4[J]. Comput Struct Biotechnol J, 2023, 21: 3680- 3689. DOI: 10.1016/j.csbj.2023.07.026.
    [16]
    KIM YS, HURLEY EH, PARK Y, et al. Primary sclerosing cholangitis(PSC) and inflammatory bowel disease(IBD): A condition exemplifying the crosstalk of the gut-liver axis[J]. Exp Mol Med, 2023, 55( 7): 1380- 1387. DOI: 10.1038/s12276-023-01042-9.
    [17]
    KUMMEN M, THINGHOLM LB, RÜHLEMANN MC, et al. Altered gut microbial metabolism of essential nutrients in primary sclerosing cholangitis[J]. Gastroenterology, 2021, 160( 5): 1784- 1798. e 0. DOI: 10.1053/j.gastro.2020.12.058.
    [18]
    KOTLYAROV S. Importance of the gut microbiota in the gut-liver axis in normal and liver disease[J]. World J Hepatol, 2024, 16( 6): 878- 882. DOI: 10.4254/wjh.v16.i6.878.
    [19]
    BIAGIOLI M, CARINO A, FIORUCCI C, et al. GPBAR1 functions as gatekeeper for liver NKT cells and provides counterregulatory signals in mouse models of immune-mediated hepatitis[J]. Cell Mol Gastroenterol Hepatol, 2019, 8( 3): 447- 473. DOI: 10.1016/j.jcmgh.2019.06.003.
    [20]
    PAIK D, YAO LN, ZHANG YC, et al. Human gut bacteria produce ΤΗ17-modulating bile acid metabolites[J]. Nature, 2022, 603( 7903): 907- 912. DOI: 10.1038/s41586-022-04480-z.
    [21]
    ZHANG L, YANG L, CHU HK. Targeting gut microbiota for the treatment of primary biliary cholangitis: From bench to bedside[J]. J Clin Transl Hepatol, 2023, 11( 4): 958- 966. DOI: 10.14218/JCTH.2022.00408.
    [22]
    LIWINSKI T, ZENOUZI R, JOHN C, et al. Alterations of the bile microbiome in primary sclerosing cholangitis[J]. Gut, 2020, 69( 4): 665- 672. DOI: 10.1136/gutjnl-2019-318416.
    [23]
    JIANG BR, YUAN GH, WU JL, et al. Prevotella copri ameliorates cholestasis and liver fibrosis in primary sclerosing cholangitis by enhancing the FXR signalling pathway[J]. Biochim Biophys Acta Mol Basis Dis, 2022, 1868( 3): 166320. DOI: 10.1016/j.bbadis.2021.166320.
    [24]
    RAHIMPOUR S, NASIRI-TOOSI M, KHALILI H, et al. A triple blinded, randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of oral vancomycin in primary sclerosing cholangitis: A pilot study[J]. J Gastrointestin Liver Dis, 2016, 25( 4): 457- 464. DOI: 10.15403/jgld.2014.1121.254.rah.
    [25]
    BRITTO SL, HOFFMAN KL, TESSIER ME, et al. Microbiome responses to vancomycin treatment in a child with primary sclerosing cholangitis and ulcerative colitis[J]. ACG Case Rep J, 2021, 8( 5): e00577. DOI: 10.14309/crj.0000000000000577.
    [26]
    FÄRKKILÄ M, KARVONEN AL, NURMI H, et al. Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: A randomized placebo-controlled trial[J]. Hepatology, 2004, 40( 6): 1379- 1386. DOI: 10.1002/hep.20457.
    [27]
    di GIORGIO A, TULONE A, NICASTRO E, et al. Use of oral vancomycin in children with autoimmune liver disease: A single centre experience[J]. World J Hepatol, 2021, 13( 12): 2113- 2127. DOI: 10.4254/wjh.v13.i12.2113.
    [28]
    LI LP, KANG YB. The gut microbiome and autoimmune hepatitis: Implications for early diagnostic biomarkers and novel therapies[J]. Mol Nutr Food Res, 2023, 67( 24): e2300043. DOI: 10.1002/mnfr.20-2300043.
    [29]
    PHILIPS CA, AUGUSTINE P, PHADKE N. Healthy donor fecal microbiota transplantation for recurrent bacterial cholangitis in primary sclerosing cholangitis- a single case report[J]. J Clin Transl Hepatol, 2018, 6( 4): 438- 441. DOI: 10.14218/JCTH.2018.00033.
    [30]
    ALLEGRETTI JR, KASSAM Z, CARRELLAS M, et al. Fecal microbiota transplantation in patients with primary sclerosing cholangitis: A pilot clinical trial[J]. Am J Gastroenterol, 2019, 114( 7): 1071- 1079. DOI: 10.14309/ajg.0000000000000115.
    [31]
    JIA W, LI YT, CHEUNG KCP, et al. Bile acid signaling in the regulation of whole body metabolic and immunological homeostasis[J]. Sci China Life Sci, 2024, 67( 5): 865- 878. DOI: 10.1007/s11427-023-2353-0.
    [32]
    ZHANG HX, LIU M, LIU X, et al. Bifidobacterium animalis ssp. lactis 420 mitigates autoimmune hepatitis through regulating intestinal barrier and liver immune cells[J]. Front Immunol, 2020, 11: 569104. DOI: 10.3389/fimmu.2020.569104.
    [33]
    MA L, ZHANG LW, ZHUANG Y, et al. Lactobacillus improves the effects of prednisone on autoimmune hepatitis via gut microbiota-mediated follicular helper T cells[J]. Cell Commun Signal, 2022, 20( 1): 83. DOI: 10.1186/s12964-021-00819-7.
    [34]
    KANG YB, KUANG XY, YAN H, et al. A novel synbiotic alleviates autoimmune hepatitis by modulating the gut microbiota-liver axis and inhibiting the hepatic TLR4/NF-κB/NLRP3 signaling pathway[J]. mSystems, 2023, 8( 2). DOI: 10.1128/msystems.01127-22.
    [35]
    RODRÍGUEZ-PASTÉN A, PÉREZ-HERNÁNDEZ N, AÑORVE-MORGA J, et al. The activity of prebiotics and probiotics in hepatogastrointestinal disorders and diseases associated with metabolic syndrome[J]. Int J Mol Sci, 2022, 23( 13): 7229. DOI: 10.3390/ijms23137229.
    [36]
    BOGATIC D, BRYANT RV, LYNCH KD, et al. Systematic review: Microbial manipulation as therapy for primary sclerosing cholangitis[J]. Aliment Pharmacol Ther, 2023, 57( 1): 23- 36. DOI: 10.1111/apt.17251.
    [37]
    LI C, NIU ZH, ZOU MJ, et al. Probiotics, prebiotics, and synbiotics regulate the intestinal microbiota differentially and restore the relative abundance of specific gut microorganisms[J]. J Dairy Sci, 2020, 103( 7): 5816- 5829. DOI: 10.3168/jds.2019-18003.
    [38]
    HUANG GF, YANG JH. Relationship between autoantibodies and biochemical responses to different doses of ursodeoxycholic acid for the treatment of primary biliary cholangitis[J]. Med J Chin People’s Liberat Army, 2022, 47( 2): 143- 149. DOI: 10.11855/j.issn.0577-7402.2022.02.0143.

    黄桂芳, 杨晋辉. 自身抗体与熊去氧胆酸治疗原发性胆汁性胆管炎生化应答的关系探讨[J]. 解放军医学杂志, 2022, 47( 2): 143- 149. DOI: 10.11855/j.issn.0577-7402.2022.02.0143.
    [39]
    Chinese Society of Hepatology, Chinese Medical Association. Guideline on the management of cholestasis liver diseases(2021)[J]. J Clin Hepatol, 2022, 38( 1): 62- 69. DOI: 10.3969/j.issn.1001-5256.2022.01.010.

    中华医学会肝病学分会. 胆汁淤积性肝病管理指南(2021)[J]. 临床肝胆病杂志, 2022, 38( 1): 62- 69. DOI: 10.3969/j.issn.1001-5256.2022.01.010.
    [40]
    WU JW, LYU SX, GUO D, et al. Protective effects of YCHD on the autoimmune hepatitis mice model induced by Ad-CYP2D6 through modulating the Th1/Treg ratio and intestinal flora[J]. Front Immunol, 2024, 15: 1488125. DOI: 10.3389/fimmu.2024.1488125.
    [41]
    ZHOU XH, GONG DY, ZHONG S. Protective effect of modified Yinchenhao decoction against acute liver injury in rats by inhibiting TLR4 signaling pathway[J]. J Shanxi Med Univ, 2021, 52( 9): 1143- 1148. DOI: 10.13753/j.issn.1007-6611.2021.09.009.

    周兴华, 龚道银, 钟森. 加味茵陈蒿汤通过抑制TLR4信号通路对大鼠急性肝损伤的保护作用[J]. 山西医科大学学报, 2021, 52( 9): 1143- 1148. DOI: 10.13753/j.issn.1007-6611.2021.09.009.
    [42]
    YANG H, LIU QQ, LIU HX, et al. Berberine alleviates concanavalin A-induced autoimmune hepatitis in mice by modulating the gut microbiota[J]. Hepatol Commun, 2024, 8( 4): e0381. DOI: 10.1097/HC9.0000000000000381.
    [43]
    ZENG X, LIU MH, XIONG Y, et al. Pien Tze Huang alleviates Concanavalin A-induced autoimmune hepatitis by regulating intestinal microbiota and memory regulatory T cells[J]. World J Gastroenterol, 2023, 29( 45): 5988- 6016. DOI: 10.3748/wjg.v29.i45.5988.
    [44]
    Expert Committee on Hepatology, Doctor Society of Integrative Medicine, Chinese Medical Doctor Association. Experts consensus on integrated traditional Chinese and Western medicine diagnosis and treatment of primary biliary cholangitis[J]. J Clin Hepatol, 2024, 40( 9): 1757- 1766. DOI: 10.12449/JCH240907.

    中国医师协会中西医结合医师分会肝病学专家委员会. 原发性胆汁性胆管炎中西医结合诊疗专家共识[J]. 临床肝胆病杂志, 2024, 40( 9): 1757- 1766. DOI: 10.12449/JCH240907.
    [45]
    GÓRSKI A, JOŃCZYK-MATYSIAK E, ŁUSIAK-SZELACHOWSKA M, et al. Therapeutic potential of phages in autoimmune liver diseases[J]. Clin Exp Immunol, 2018, 192( 1): 1- 6. DOI: 10.1111/cei.13092.
    [46]
    NIE QX, LUO X, WANG K, et al. Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway[J]. Cell, 2024, 187( 11): 2717- 2734. e 33. DOI: 10.1016/j.cell.2024.03.034.
    [47]
    FUJIKI J, SCHNABL B. Phage therapy: Targeting intestinal bacterial microbiota for the treatment of liver diseases[J]. JHEP Rep, 2023, 5( 12): 100909. DOI: 10.1016/j.jhepr.2023.100909.
    [48]
    WU ZH, SUN Y, HUANG WB, et al. Direct and indirect effects of estrogens, androgens and intestinal microbiota on colorectal cancer[J]. Front Cell Infect Microbiol, 2024, 14: 1458033. DOI: 10.3389/fcimb.2024.1458033.
    [49]
    ZHANG HX, LIU M, LIU X, et al. Bifidobacterium animalis ssp. lactis 420 mitigates autoimmune hepatitis through regulating intestinal barrier and liver immune cells[J]. Front Immunol, 2020, 11: 569104. DOI: 10.3389/fimmu.2020.569104.
    [50]
    ZU Y, YANG JY, ZHANG CL, et al. The pathological mechanisms of estrogen-induced cholestasis: Current perspectives[J]. Front Pharmacol, 2021, 12: 761255. DOI: 10.3389/fphar.2021.761255.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(1)  / Tables(1)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (47) PDF downloads(21) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return