Advances in role of gut-liver axis in non-alcoholic fatty liver disease

DING Mingxia; LUO Yawen; HE Yihuai

doi:10.7619/jcmp.20245704

Journal of Clinical Medicine in Practice > 2025 > 29(7): 143-148. > DOI: 10.7619/jcmp.20245704

DING Mingxia, LUO Yawen, HE Yihuai. Advances in role of gut-liver axis in non-alcoholic fatty liver disease[J]. Journal of Clinical Medicine in Practice, 2025, 29(7): 143-148. DOI: 10.7619/jcmp.20245704

Citation:

PDF (785 KB)

Advances in role of gut-liver axis in non-alcoholic fatty liver disease

Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000

More Information

Received Date: November 19, 2024
Revised Date: February 12, 2025

Graphical Abstract

Abstract

Abstract

The gut-liver axis is critical pathway of interaction between the intestine and the liver, involving gut microbiota, intestinal permeability and immune responses.Dysbiosis of the gut microbiota and increased intestinal permeability lead to the translocation of bacteria and their metabolites into the systemic circulation, thereby triggering hepatic inflammation and promoting the progression of non-alcoholic fatty liver disease (NAFLD).Research on the gut-liver axis contributes to the development of novel therapeutic approaches, including fecal microbiota transplantation, antibiotic therapy and nutritional intervention, providing new insights for the treatment of NAFLD.This article reviewed the composition and regulatory mechanism of entero-hepatic axis, its relationship with NAFLD, and the role of drug therapy and lifestyle intervention.
- non-alcoholic fatty liver disease,
- gut,
- liver,
- gut-liver axis,
- gut microbiota,
- metabolites,
- immune response,
- microbiota transplantation

FullText(HTML)

References (51)

References

[1]	BENEDICT M, ZHANG X C. Non-alcoholic fatty liver disease: an expanded review[J]. World J Hepatol, 2017, 9(16): 715-732. doi: 10.4254/wjh.v9.i16.715
[2]	YOUNOSSI Z M, GOLABI P, PAIK J M, et al. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review[J]. Hepatology, 2023, 77(4): 1335-1347. doi: 10.1097/HEP.0000000000000004
[3]	LI J, HA A, RUI F J, et al. Meta-analysis: global prevalence, trend and forecasting of non-alcoholic fatty liver disease in children and adolescents, 2000—2021[J]. Aliment Pharmacol Ther, 2022, 56(3): 396-406. doi: 10.1111/apt.17096
[4]	LIU H X, QI J L, YANG J, et al. Burden of liver complications related to non-alcoholic fatty liver disease in China from 2005 to 2019: Observations from the Global Burden of Disease Study, 2019[J]. Diabetes Obes Metab, 2023, 25(Suppl 1): 43-52.
[5]	范建高, 徐小元, 南月敏, 等. 代谢相关(非酒精性)脂肪性肝病防治指南(2024年版)[J]. 实用肝脏病杂志, 2024, 27(4): 494-510.
[6]	MAHMOUDI S K, TARZEMANI S, AGHAJANZADEH T, et al. Exploring the role of genetic variations in NAFLD: implications for disease pathogenesis and precision medicine approaches[J]. Eur J Med Res, 2024, 29(1): 190. doi: 10.1186/s40001-024-01708-8
[7]	ZHENG Y W, WANG S T, WU J L, et al. Mitochondrial metabolic dysfunction and non-alcoholic fatty liver disease: new insights from pathogenic mechanisms to clinically targeted therapy[J]. J Transl Med, 2023, 21(1): 510. doi: 10.1186/s12967-023-04367-1
[8]	MOURIES J, BRESCIA P, SILVESTRI A, et al. Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development[J]. J Hepatol, 2019, 71(6): 1216-1228. doi: 10.1016/j.jhep.2019.08.005
[9]	KE Z L, HUANG Y B, XU J, et al. Escherichia coli NF73-1 disrupts the gut-vascular barrier and aggravates high-fat diet-induced fatty liver disease via inhibiting Wnt/β-catenin signalling pathway[J]. Liver Int, 2024, 44(3): 776-790. doi: 10.1111/liv.15823
[10]	王芳昭, 崔茜如, 曾雨浓, 等. 肠道菌群: 肝脏疾病的重要参与者[J]. 南方医科大学学报, 2020, 40(4): 595-600.
[11]	PABST O, HORNEF M W, SCHAAP F G, et al. Gut-liver axis: barriers and functional circuits[J]. Nat Rev Gastroenterol Hepatol, 2023, 20(7): 447-461. doi: 10.1038/s41575-023-00771-6
[12]	KUMAR A R, NAIR B, KAMATH A J, et al. Impact of gut microbiota on metabolic dysfunction-associated steatohepatitis and hepatocellular carcinoma: pathways, diagnostic opportunities and therapeutic advances[J]. Eur J Med Res, 2024, 29(1): 485. doi: 10.1186/s40001-024-02072-3
[13]	YANG X Y, LU D, ZHUO J Y, et al. The gut-liver axis in immune remodeling: new insight into liver diseases[J]. Int J Biol Sci, 2020, 16(13): 2357-2366. doi: 10.7150/ijbs.46405
[14]	ZHOU C X, SUN L D, HU G Q, et al. Discovery of novel glucagon-like peptide 1/cholecystokinin 1 receptor dual agonists[J]. Eur J Pharm Sci, 2024, 199: 106818. doi: 10.1016/j.ejps.2024.106818
[15]	范圣先, 王剑, 李强, 等. 肠-菌-肝轴及其在肠衰竭相关性肝损害发生发展中的作用[J]. 中华胃肠外科杂志, 2021, 24(1): 94-100.
[16]	MILOSEVIC I, VUJOVIC A, BARAC A, et al. Gut-liver axis, gut microbiota, and its modulation in the management of liver diseases: a review of the literature[J]. Int J Mol Sci, 2019, 20(2): 395. doi: 10.3390/ijms20020395
[17]	NOUREDDIN M, SANYAL A J. Pathogenesis of NASH: the impact of multiple pathways[J]. Curr Hepatol Rep, 2018, 17(4): 350-360. doi: 10.1007/s11901-018-0425-7
[18]	VANCELLS LUJAN P, VIÑAS ESMEL E, SACANELLA MESEGUER E. Overview of non-alcoholic fatty liver disease (NAFLD) and the role of sugary food consumption and other dietary components in its development[J]. Nutrients, 2021, 13(5): 1442. doi: 10.3390/nu13051442
[19]	WANG H, MEHAL W, NAGY L E, et al. Immunological mechanisms and therapeutic targets of fatty liver diseases[J]. Cell Mol Immunol, 2021, 18(1): 73-91. doi: 10.1038/s41423-020-00579-3
[20]	YAN M Y, MAN S L, MA L, et al. Immunological mechanisms in steatotic liver diseases: an overview and clinical perspectives[J]. Clin Mol Hepatol, 2024, 30(4): 620-648. doi: 10.3350/cmh.2024.0315
[21]	LOCATELLI I, SUTTI S, VACCHIANO M, et al. NF-κB1 deficiency stimulates the progression of non-alcoholic steatohepatitis (NASH) in mice by promoting NKT-cell-mediated responses[J]. Clin Sci (Lond), 2013, 124(4): 279-287. doi: 10.1042/CS20120289
[22]	ORTIZ-LÓPEZ N, MADRID A M, ALEMAN L, et al. Small intestinal bacterial overgrowth in obese patients with biopsy-confirmed metabolic dysfunction-associated steatotic liver disease: a cross-sectional study[J]. Front Med (Lausanne), 2024, 11: 1376148.
[23]	SURIANO F, VIEIRA-SILVA S, FALONY G, et al. Novel insights into the genetically obese (ob/ob) and diabetic (db/db) mice: two sides of the same coin[J]. Microbiome, 2021, 9(1): 147. doi: 10.1186/s40168-021-01097-8
[24]	KIM M H, KIM H. Role of leptin in the digestive system[J]. Front Pharmacol, 2021, 12: 660040. doi: 10.3389/fphar.2021.660040
[25]	GAO Y, LI W J, HUANG X Y, et al. Advances in gut microbiota-targeted therapeutics for metabolic syndrome[J]. Microorganisms, 2024, 12(5): 851. doi: 10.3390/microorganisms12050851
[26]	中华医学会肠外肠内营养学分会. 中国成人患者微营养素临床应用指南(2024版)[J]. 中华医学杂志, 2024, 104(11): 799-821.
[27]	COBO E R, KISSOON-SINGH V, MOREAU F, et al. MUC2 mucin and butyrate contribute to the synthesis of the antimicrobial peptide cathelicidin in response to Entamoeba histolytica- and dextran sodium sulfate-induced colitis[J]. Infect Immun, 2017, 85(3): e00905-16.
[28]	FEI N, BRUNEAU A, ZHANG X J, et al. Endotoxin producers overgrowing in human gut microbiota as the causative agents for nonalcoholic fatty liver disease[J]. mBio, 2020, 11(1): e03263-19.
[29]	惠登城, 孙明瑜. 基于肠-肝轴理论探讨非酒精性脂肪性肝病和肠道菌群的关系[J]. 临床肝胆病杂志, 2020, 36(7): 1627-1630.
[30]	RAMANAN S P, MOHAMED M W F, AUNG S S, et al. Treatment of fatty liver disease: the present and the future[J]. Cureus, 2021, 13(1): e12713.
[31]	DONG X, XIONG Y T, HE T T, et al. Protective effects of Nogo-B deficiency in NAFLD mice and its multiomics analysis of gut microbiology and metabolism[J]. Genes Nutr, 2024, 19(1): 17. doi: 10.1186/s12263-024-00754-5
[32]	孔弘伟. 抗幽门螺杆菌(Hp)治疗对非酒精性脂肪性肝病伴Hp感染患者的疗效[J]. 实用临床医药杂志, 2019, 23(2): 60-63. doi: 10.7619/jcmp.201902017
[33]	SURIANO F, MANCA C, FLAMAND N, et al. A lipidomics- and transcriptomics-based analysis of the intestine of genetically obese (ob/ob) and diabetic (db/db) mice: links with inflammation and gut microbiota[J]. Cells, 2023, 12(3): 411. doi: 10.3390/cells12030411
[34]	ELAMIN E E, MASCLEE A A, DEKKER J, et al. Ethanol metabolism and its effects on the intestinal epithelial barrier[J]. Nutr Rev, 2013, 71(7): 483-499. doi: 10.1111/nure.12027
[35]	MACCIONI L, FU Y J, HORSMANS Y, et al. Alcohol-associated bowel disease: new insights into pathogenesis[J]. eGastroenterology, 2023, 1(1): e100013. doi: 10.1136/egastro-2023-100013
[36]	KUO W T, ZUO L, ODENWALD M A, et al. The tight junction protein ZO-1 is dispensable for barrier function but critical for effective mucosal repair[J]. Gastroenterology, 2021, 161(6): 1924-1939. doi: 10.1053/j.gastro.2021.08.047
[37]	JI Y, YIN Y, SUN L J, et al. The molecular and mechanistic insights based on gut-liver axis: nutritional target for non-alcoholic fatty liver disease (NAFLD) improvement[J]. Int J Mol Sci, 2020, 21(9): 3066. doi: 10.3390/ijms21093066
[38]	FAN Y, PEDERSEN O. Gut microbiota in human metabolic health and disease[J]. Nat Rev Microbiol, 2021, 19(1): 55-71. doi: 10.1038/s41579-020-0433-9
[39]	HOWARD E J, LAM T K T, DUCA F A. The gut microbiome: connecting diet, glucose homeostasis, and disease[J]. Annu Rev Med, 2022, 73: 469-481. doi: 10.1146/annurev-med-042220-012821
[40]	LI X Y, HE M Z, YI X R, et al. Short-chain fatty acids in nonalcoholic fatty liver disease: New prospects for short-chain fatty acids as therapeutic targets[J]. Heliyon, 2024, 10(5): e26991. doi: 10.1016/j.heliyon.2024.e26991
[41]	KUMAR J, RANI K, DATT C. Molecular link between dietary fibre, gut microbiota and health[J]. Mol Biol Rep, 2020, 47(8): 6229-6237. doi: 10.1007/s11033-020-05611-3
[42]	SZUDZIK M, HUTSCH T, CHABOWSKI D, et al. Normal caloric intake with high-fat diet induces metabolic dysfunction-associated steatotic liver disease and dyslipidemia without obesity in rats[J]. Sci Rep, 2024, 14(1): 22796. doi: 10.1038/s41598-024-74193-y
[43]	YADEGAR A, BAR-YOSEPH H, MONAGHAN T M, et al. Fecal microbiota transplantation: current challenges and future landscapes[J]. Clin Microbiol Rev, 2024, 37(2): e0006022. doi: 10.1128/cmr.00060-22
[44]	GHANI R, CHRYSOSTOMOU D, ROBERTS L A, et al. Faecal (or intestinal) microbiota transplant: a tool for repairing the gut microbiome[J]. Gut Microbes, 2024, 16(1): 2423026. doi: 10.1080/19490976.2024.2423026
[45]	JIANG L, STÖRKEL P, FAN J G, et al. The gut mycobiome: a novel player in chronic liver diseases[J]. J Gastroenterol, 2021, 56(1): 1-11. doi: 10.1007/s00535-020-01740-5
[46]	国家卫生健康委员会医院管理研究所, 中华医学会肠外肠内营养学分会, 中华医学会肠外肠内营养学分会肠道微生态协作组. 肠道菌群移植临床应用管理中国专家共识(2022版)[J]. 中华胃肠外科杂志, 2022, 25(9): 747-756.
[47]	QU Z H, TIAN P J, YANG B, et al. Fecal microbiota transplantation for diseases: therapeutic potential, methodology, risk management in clinical practice[J]. Life Sci, 2022, 304: 120719. doi: 10.1016/j.lfs.2022.120719
[48]	BARROSO E, MONTORI-GRAU M, WAHLI W, et al. Striking a gut-liver balance for the antidiabetic effects of metformin[J]. Trends Pharmacol Sci, 2023, 44(7): 457-473. doi: 10.1016/j.tips.2023.04.004
[49]	TONG L J, ZHANG S T, LIU Q Q, et al. Milk-derived extracellular vesicles protect intestinal barrier integrity in the gut-liver axis[J]. Sci Adv, 2023, 9(15): eade5041. doi: 10.1126/sciadv.ade5041
[50]	SARKAR A, MITRA P, LAHIRI A, et al. Butyrate limits inflammatory macrophage niche in NASH[J]. Cell Death Dis, 2023, 14(5): 332. doi: 10.1038/s41419-023-05853-6
[51]	刘雨, 牛淑利, 李梦月, 等. 姜黄素治疗非酒精性脂肪性肝病的研究进展[J]. 实用临床医药杂志, 2021, 25(5): 118-124. doi: 10.7619/jcmp.20200328

Cited By

Get Citation

PDF

XML

Article views (37) PDF downloads (8)

Turn off MathJax

Article Contents

Abstract

References

Advances in role of gut-liver axis in non-alcoholic fatty liver disease

Abstract

References

Catalog

Export File

Citation

Format

Content