肠道微生态与自身免疫性肝炎发生发展的关系

夏雨艳; 曾琼戎; 李福建; 黎凤炎; 李琪; 唐利瑕; 张国

doi:10.12449/JCH240225

肠道微生态与自身免疫性肝炎发生发展的关系

DOI: 10.12449/JCH240225

1.
广西医科大学研究生院，南宁 530000
2.
中山大学附属第一医院广西医院消化内科，南宁 530000
3.
广西壮族自治区人民医院（广西医学科学院）消化内科，南宁 530000

基金项目:

广西科技计划项目 (AD17129027);

广西壮族自治区卫生健康委员会重点（培育）实验室 (ZZH2020006)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：夏雨艳负责查阅文献，起草论文；黎凤炎、李琪、唐利瑕参与部分内容撰写；张国、李福建、曾琼戎拟定写作思路，指导和修改论文，核对有关文献并最后定稿。

详细信息

通信作者:
张国， zhangguogx@hotmail.com （ORCID： 0000-0001-7755-443X）

计量
- 文章访问数: 341
- HTML全文浏览量: 103
- PDF下载量: 64
- 被引次数: 0
出版历程
- 收稿日期: 2023-06-20
- 录用日期: 2023-07-11
- 出版日期: 2024-02-19

Association of intestinal microecology with the development and progression of autoimmune hepatitis

1.
Graduate School，Guangxi Medical University，Nanning 530000，China
2.
Department of Gastroenterology，Guangxi Hospital Division of The First Affiliated Hospital，Sun Yat-sen University，Nanning 530000，China
3.
Department of Gastroenterology，The People’s Hospital of Guangxi Zhuang Autonomous Region/Guangxi Academy of Medical Sciences，Nanning 530000，China

Research funding:

Guangxi Science and Technology Program Project (AD17129027);

Key （Cultivation） Laboratory of Health Commission of Guangxi Zhuang Autonomous Region (ZZH2020006)

More Information

Corresponding author: ZHANG Guo， zhangguogx@hotmail.com （ORCID： 0000-0001-7755-443X）

摘要

摘要: 自身免疫性肝炎（AIH）是以慢性肝脏炎症为特点的自身免疫性疾病，发病率逐年升高，社会医疗负担不容小视。肠道微生态正成为自身免疫性疾病研究的热点。近年来认为肠道微生态的改变会引起自身免疫状态、菌群代谢产物和肠道屏障的改变，是AIH发病的驱动因素之一。早期诊断和正确的治疗有助于改善AIH患者的预后。本文介绍了AIH患者肠道菌群的特点、肠道微生态失衡对AIH发病机制的影响以及从肠道微生态角度出发简述了相关治疗方案，旨在全面理解和解释肠道微生态在AIH中的作用，了解肠道微生态平衡对AIH致病机制、诊断和治疗的影响。
- 肝炎，自身免疫性 /
- 胃肠道微生物组 /
- 诊断 /
- 治疗
Abstract: Autoimmune hepatitis （AIH） is an autoimmune disease characterized by chronic liver inflammation， with a gradually increasing incidence rate， and its social and medical burdens cannot be neglected. Intestinal microecology is becoming a research hotspot in the field of autoimmune disease. In recent years， it has been believed that changes in intestinal microecology can cause changes in autoimmune state， microbial metabolites， and intestinal barrier， which is one of the driving factors for the onset of AIH. Early diagnosis and correct treatment can help to improve the prognosis of AIH patients. This article introduces the characteristics of gut microbiota in AIH patients， elaborates on the impact of intestinal microflora imbalance on the pathogenesis of AIH， and briefly describes related treatment regimens from the perspective of intestinal microecology， so as to comprehensively understand and explain the role of intestinal microecology in AIH and the impact of intestinal microecology balance on the pathogenesis， diagnosis， and treatment of AIH.
- Hepatitis， Autoimmune /
- Gastrointestinal Microbiome /
- Diagnosis /
- Therapeutics

HTML全文

参考文献(45)

[1]	Chinese Society of Hepatology, Chinese Medical Association. Guidelines on the diagnosis and management of autoimmune hepatitis(2021)[J]. J Clin Hepatol, 2022, 38( 1): 42- 49. DOI: 10.3969/j.issn.1001-5256.2022.01.008. 中华医学会肝病学分会. 自身免疫性肝炎诊断和治疗指南(2021)[J]. 临床肝胆病杂志, 2022, 38( 1): 42- 49. DOI: 10.3969/j.issn.1001-5256.2022.01.008.
[2]	PUUSTINEN L, BARNER-RASMUSSEN N, PUKKALA E, et al. Incidence, prevalence, and causes of death of patients with autoimmune hepatitis: A nationwide register-based cohort study in Finland[J]. Dig Liver Dis, 2019, 51( 9): 1294- 1299. DOI: 10.1016/j.dld.2019.01.015.
[3]	GRØNBAEK L, OTETE H, BAN L, et al. Incidence, prevalence and mortality of autoimmune hepatitis in England 1997-2015. A population-based cohort study[J]. Liver Int, 2020, 40( 7): 1634- 1644. DOI: 10.1111/liv.14480.
[4]	LAMBA M, NGU JH, STEDMAN CAM. Trends in incidence of autoimmune liver diseases and increasing incidence of autoimmune hepatitis[J]. Clin Gastroenterol Hepatol, 2021, 19( 3): 573- 579. DOI: 10.1016/j.cgh.2020.05.061.
[5]	TRIVEDI PJ, HIRSCHFIELD GM. Recent advances in clinical practice: Epidemiology of autoimmune liver diseases[J]. Gut, 2021, 70( 10): 1989- 2003. DOI: 10.1136/gutjnl-2020-322362.
[6]	FLOREANI A, RESTREPO-JIMÉNEZ P, SECCHI MF, et al. Etiopathogenesis of autoimmune hepatitis[J]. J Autoimmun, 2018, 95: 133- 143. DOI: 10.1016/j.jaut.2018.10.020.
[7]	TORRES J, HU JZ, SEKI A, et al. Infants born to mothers with IBD present with altered gut microbiome that transfers abnormalities of the adaptive immune system to germ-free mice[J]. Gut, 2020, 69( 1): 42- 51. DOI: 10.1136/gutjnl-2018-317855.
[8]	NABHANI Z AL, EBERL G. Imprinting of the immune system by the microbiota early in life[J]. Mucosal Immunol, 2020, 13( 2): 183- 189. DOI: 10.1038/s41385-020-0257-y.
[9]	BOULUND U, BASTOS DM, FERWERDA B, et al. Gut microbiome associations with host genotype vary across ethnicities and potentially influence cardiometabolic traits[J]. Cell Host Microbe, 2022, 30( 10): 1464- 1480. DOI: 10.1016/j.chom.2022.08.013.
[10]	LEE BT, TANA MM, KAHN JA, et al. We are not immune: Racial and ethnic disparities in autoimmune liver diseases[J]. Hepatology, 2021, 74( 5): 2876- 2887. DOI: 10.1002/hep.31985.
[11]	LYNCH SV, PEDERSEN O. The human intestinal microbiome in health and disease[J]. N Engl J Med, 2016, 375( 24): 2369- 2379. DOI: 10.1056/NEJMra1600266.
[12]	TERZIROLI BERETTA-PICCOLI B, MIELI-VERGANI G, VERGANI D. Autoimmmune hepatitis[J]. Cell Mol Immunol, 2022, 19( 2): 158- 176. DOI: 10.1038/s41423-021-00768-8.
[13]	WEI YR, LI YM, YAN L, et al. Alterations of gut microbiome in autoimmune hepatitis[J]. Gut, 2020, 69( 3): 569- 577. DOI: 10.1136/gutjnl-2018-317836.
[14]	LOU JM, JIANG Y, RAO BC, et al. Fecal microbiomes distinguish patients with autoimmune hepatitis from healthy individuals[J]. Front Cell Infect Microbiol, 2020, 10: 342. DOI: 10.3389/fcimb.2020.00342.
[15]	LIWINSKI T, CASAR C, RUEHLEMANN MC, et al. A disease-specific decline of the relative abundance of Bifidobacterium in patients with autoimmune hepatitis[J]. Aliment Pharmacol Ther, 2020, 51( 12): 1417- 1428. DOI: 10.1111/apt.15754.
[16]	WANG H, BANERJEE N, LIANG YJ, et al. Gut microbiome-host interactions in driving environmental pollutant trichloroethene-mediated autoimmunity[J]. Toxicol Appl Pharmacol, 2021, 424: 115597. DOI: 10.1016/j.taap.2021.115597.
[17]	WANG H, WANG Q, YANG CM, et al. Bacteroides acidifaciens in the gut plays a protective role against CD95-mediated liver injury[J]. Gut Microbes, 2022, 14( 1): 2027853. DOI: 10.1080/19490976.2022.2027853.
[18]	CHEN JN, LI XH, ZENG P, et al. Lamina propria interleukin 17 A aggravates natural killer T-cell activation in autoimmune hepatitis[J]. FASEB J, 2022, 36( 6): e22346. DOI: 10.1096/fj.202101734RRR.
[19]	CENTA M, WEINSTEIN EG, CLEMENTE JC, et al. Impaired central tolerance induces changes in the gut microbiota that exacerbate autoimmune hepatitis[J]. J Autoimmun, 2022, 128: 102808. DOI: 10.1016/j.jaut.2022.102808.
[20]	DALILE B, VAN OUDENHOVE L, VERVLIET B, et al. The role of short-chain fatty acids in microbiota-gut-brain communication[J]. Nat Rev Gastroenterol Hepatol, 2019, 16( 8): 461- 478. DOI: 10.1038/s41575-019-0157-3.
[21]	LIU QQ, TIAN HX, KANG YB, et al. Probiotics alleviate autoimmune hepatitis in mice through modulation of gut microbiota and intestinal permeability[J]. J Nutr Biochem, 2021, 98: 108863. DOI: 10.1016/j.jnutbio.2021.108863.
[22]	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.
[23]	BHASKARAN N, QUIGLEY C, PAW C, et al. Role of short chain fatty acids in controlling T(regs) and immunopathology during mucosal infection[J]. Front Microbiol, 2018, 9: 1995. DOI: 10.3389/fmicb.2018.01995.
[24]	HU ED, CHEN DZ, WU JL, et al. High fiber dietary and sodium butyrate attenuate experimental autoimmune hepatitis through regulation of immune regulatory cells and intestinal barrier[J]. Cell Immunol, 2018, 328: 24- 32. DOI: 10.1016/j.cellimm.2018.03.003.
[25]	WU JL, ZOU JY, HU ED, et al. Sodium butyrate ameliorates S100/FCA-induced autoimmune hepatitis through regulation of intestinal tight junction and toll-like receptor 4 signaling pathway[J]. Immunol Lett, 2017, 190: 169- 176. DOI: 10.1016/j.imlet.2017.08.005.
[26]	YANG JS, XIE WT, YU KK, et al. Methyl butyrate attenuates concanavalin A-induced autoimmune hepatitis by inhibiting Th1-cell activation and homing to the liver[J]. Cell Immunol, 2022, 378: 104575. DOI: 10.1016/j.cellimm.2022.104575.
[27]	ELSHERBINY NM, RAMMADAN M, HASSAN EA, et al. Autoimmune hepatitis: Shifts in gut microbiota and metabolic pathways among Egyptian patients[J]. Microorganisms, 2020, 8( 7): 1011. DOI: 10.3390/microorganisms8071011.
[28]	MA JL, HONG Y, ZHENG NN, et al. Gut microbiota remodeling reverses aging-associated inflammation and dysregulation of systemic bile acid homeostasis in mice sex-specifically[J]. Gut Microbes, 2020, 11( 5): 1450- 1474. DOI: 10.1080/19490976.2020.1763770.
[29]	MENCARELLI A, RENGA B, MIGLIORATI M, et al. The bile acid sensor farnesoid X receptor is a modulator of liver immunity in a rodent model of acute hepatitis[J]. J Immunol, 2009, 183( 10): 6657- 6666. DOI: 10.4049/jimmunol.0901347.
[30]	ZHANG T, RAO QR, DAI MY, et al. Tripterygium wilfordii protects against an animal model of autoimmune hepatitis[J]. J Ethnopharmacol, 2023, 309: 116365. DOI: 10.1016/j.jep.2023.116365.
[31]	LARABI AB, MASSON HLP, BÄUMLER AJ. Bile acids as modulators of gut microbiota composition and function[J]. Gut Microbes, 2023, 15( 1): 2172671. DOI: 10.1080/19490976.2023.2172671.
[32]	FUNG TC, VUONG HE, LUNA CDG, et al. Intestinal serotonin and fluoxetine exposure modulate bacterial colonization in the gut[J]. Nat Microbiol, 2019, 4( 12): 2064- 2073. DOI: 10.1038/s41564-019-0540-4.
[33]	ALMISHRI W, SHAHEEN AA, SHARKEY KA, et al. The antidepressant mirtazapine inhibits hepatic innate immune networks to attenuate immune-mediated liver injury in mice[J]. Front Immunol, 2019, 10: 803. DOI: 10.3389/fimmu.2019.00803.
[34]	XUE RF, ZHANG HM, PAN J, et al. Peripheral dopamine controlled by gut microbes inhibits invariant natural killer T cell-mediated hepatitis[J]. Front Immunol, 2018, 9: 2398. DOI: 10.3389/fimmu.2018.02398.
[35]	ZHANG HX, LIU M, ZHONG WL, et al. Leaky gut driven by dysbiosis augments activation and accumulation of liver macrophages via RIP3 signaling pathway in autoimmune hepatitis[J]. Front Immunol, 2021, 12: 624360. DOI: 10.3389/fimmu.2021.624360.
[36]	LIN HW, LIN J, PAN TT, et al. Polymeric immunoglobulin receptor deficiency exacerbates autoimmune hepatitis by inducing intestinal dysbiosis and barrier dysfunction[J]. Cell Death Dis, 2023, 14( 1): 68. DOI: 10.1038/s41419-023-05589-3.
[37]	LIN R, ZHOU L, ZHANG J, et al. Abnormal intestinal permeability and microbiota in patients with autoimmune hepatitis[J]. Int J Clin Exp Pathol, 2015, 8( 5): 5153- 5160.
[38]	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.
[39]	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): e0112722. DOI: 10.1128/msystems.01127-22.
[40]	MA L, ZHANG LW, SONG JG, et al. Fecal microbiota transplantation controls progression of experimental autoimmune hepatitis in mice by modulating the TFR/TFH immune imbalance and intestinal microbiota composition[J]. Front Immunol, 2021, 12: 728723. DOI: 10.3389/fimmu.2021.728723.
[41]	MANRIQUE P, DILLS M, YOUNG MJ. The human gut phage community and its implications for health and disease[J]. Viruses, 2017, 9( 6): 141. DOI: 10.3390/v9060141.
[42]	TOMOFUJI Y, KISHIKAWA T, MAEDA Y, et al. Whole gut virome analysis of 476 Japanese revealed a link between phage and autoimmune disease[J]. Ann Rheum Dis, 2022, 81( 2): 278- 288. DOI: 10.1136/annrheumdis-2021-221267.
[43]	SCALDAFERRI F, LOPETUSO LR, PETITO V, et al. Gelatin tannate ameliorates acute colitis in mice by reinforcing mucus layer and modulating gut microbiota composition: Emerging role for‘gut barrier protectors’ in IBD?[J]. United European Gastroenterol J, 2014, 2( 2): 113- 122. DOI: 10.1177/2050640614520867.
[44]	WU HM, WEI J, WANG K, et al. Mucus protectors: Promising therapeutic strategies for inflammatory bowel disease[J]. Med Hypotheses, 2018, 120: 55- 59. DOI: 10.1016/j.mehy.2018.08.013.
[45]	QUE W, LIN H, LI X, et al. Koumine ameliorates concanavalin A-induced autoimmune hepatitis in mice: involvement of the Nrf2, NF-κB pathways, and gut microbiota[J]. Int Immunopharmacol, 2023, 114: 109573. DOI: 10.1016/j.intimp.2022.109573.