幽门螺杆菌感染与非酒精性脂肪性肝病的相关性及潜在机制

陈丹妮; 王世令; 路红; 郑亚; 王玉平; 任茜

doi:10.12290/xhyxzz.2022-0710

幽门螺杆菌感染与非酒精性脂肪性肝病的相关性及潜在机制

doi: 10.12290/xhyxzz.2022-0710

陈丹妮^{1, 2},
王世令^{1, 2},
路红^{2, 3},
郑亚^{2, 4},
王玉平^{2, 4},
任茜^{2, 3, 4, ,}

1.
兰州大学第一临床医学院，兰州 730000
2.
兰州大学第一医院消化科，兰州 730000
3.
兰州大学第一医院消化内镜中心，兰州 730000
4.
兰州大学第一医院甘肃省胃肠病重点实验室，兰州 730000

基金项目:

甘肃省自然科学基金 21JR7RA381

甘肃省卫生行业科研计划项目 GSWSKY2020-07

兰州大学中央高校基本科研业务费 lzujbky-2021-ct17

兰州大学第一医院院内基金 ldyyyn2019-74

详细信息

通讯作者:
任茜, E-mail: ldyy_renqian@lzu.edu.cn

中图分类号: R575; R-1
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出版历程
- 收稿日期: 2022-12-11
- 录用日期: 2023-02-09
- 刊出日期: 2023-07-30

Relationship and Potential Mechanism Between Helicobacter Pylori Infection and Non-alcoholic Fatty Liver Disease

CHEN Danni^{1, 2},
WANG Shiling^{1, 2},
LU Hong^{2, 3},
ZHENG Ya^{2, 4},
WANG Yuping^{2, 4},
REN Qian^{2, 3, 4
, ,}

1.
The First Clinical Medical College of Lanzhou University, Lanzhou 730000, China
2.
Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou 730000, China
3.
Digestive Endoscope Center, The First Hospital of Lanzhou University, Lanzhou 730000, China
4.
Gansu Key Laboratory of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou 730000, China

Funds:

Natural Science Foundation of Gansu Province 21JR7RA381

Health Industry Research Project of Gansu Province GSWSKY2020-07

Fundamental Research Funds for the Central Universities lzujbky-2021-ct17

Hospital Foundation of Lanzhou University First Hospital ldyyyn2019-74

More Information

Corresponding author: REN Qian, E-mail: ldyy_renqian@lzu.edu.cn

摘要

摘要: 随着人们生活方式的改变，非酒精性脂肪性肝病(non-alcoholic fatty liver disease，NAFLD)目前已成为世界范围内最常见的肝脏疾病，并可能发展为肝硬化、肝细胞癌(hepatocellular carcinoma, HCC)，严重威胁人类健康。目前NAFLD的治疗仍以调整生活方式、控制血糖及血脂等危险因素为主，尚无有效治疗药物，因此，对于NAFLD发病机制的研究具有重要意义。近年来的研究表明，幽门螺杆菌(Helicobacter pylori, HP)感染可能通过诱发IR、改变脂质谱、促进氧化应激、改变肠道通透性和调控基因表达导致NAFLD的发生。本文就HP感染与NAFLD之间的相关性及潜在机制相关研究进展作一综述，以期为NAFLD的诊治提供新思路。
- 幽门螺杆菌 /
- 非酒精性脂肪性肝病 /
- 胰岛素抵抗 /
- 肠道菌群
Abstract: Since people's lifestyles have changed, non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent liver condition globally. It can progress to cirrhosis and hepatocellular carcinoma (HCC), both of which pose major risks to people's health. Currently, the treatment of NAFLD is still based on lifestyle modification, glycemic and lipid control, and other risk factors, and there are no effective therapeutic drugs. Therefore, it is important to study the pathogenesis of NAFLD. Recent studies have shown that Helicobacter pylori (HP) infection is associated with the development of NAFLD, and HP infection may contribute to the development of NAFLD by inducing insulin resistance, altering the lipid profile, promoting oxidative stress, changing intestinal permeability, and regulating gene expression. Therefore, this paper reviews the correlation between HP infection and NAFLD and the potential pathogenesis of NAFLD due to HP infection, with the aim of providing new ideas for the diagnosis and treatment of NAFLD.
- Helicobacter pylori /
- non-alcoholic fatty liver disease /
- insulin resistance /
- intestinal flora
注释:

作者贡献：陈丹妮、王世令负责查阅文献及论文撰写; 路红、郑亚、王玉平负责论文修订; 任茜负责设计选题和论文审校。

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参考文献(67)

[1]	Younossi ZM, Marchesini G, Pinto-Cortez H, et al. Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: Implications for Liver Transplantation[J]. Transplantation, 2019, 103: 22-27. doi: 10.1097/TP.0000000000002484
[2]	Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)[J]. Metabolism, 2016, 65: 1038-1048. doi: 10.1016/j.metabol.2015.12.012
[3]	Negi CK, Babica P, Bajard L, et al. Insights into the molecular targets and emerging pharmacotherapeutic interven-tions for nonalcoholic fatty liver disease[J]. Metabolism, 2022, 126: 154925. doi: 10.1016/j.metabol.2021.154925
[4]	Santos MLC, De Brito BB, Da Silva FAF, et al. Helicobacter pylori infection: Beyond gastric manifestations[J]. World J Gastroenterol, 2020, 26: 4076-4093. doi: 10.3748/wjg.v26.i28.4076
[5]	Cindoruk M, Cirak MY, Unal S, et al. Identification of Helicobacter species by 16S rDNA PCR and sequence analysis in human liver samples from patients with various etiologies of benign liver diseases[J]. Eur J Gastroenterol Hepatol, 2008, 20: 33-36. doi: 10.1097/MEG.0b013e3282efa4f2
[6]	He C, Cheng D, Wang H, et al. Helicobacter pylori infection aggravates diet-induced nonalcoholic fatty liver in mice[J]. Clin Res Hepatol Gastroenterol, 2018, 42: 360-367. doi: 10.1016/j.clinre.2017.12.008
[7]	Abo-Amer YE, Sabal A, Ahmed R, et al. Relationship Between Helicobacter pylori Infection and Nonalcoholic Fatty Liver Disease (NAFLD) in a Developing Country: A Cross-Sectional Study[J]. Diabetes Metab Syndr Obes, 2020, 13: 619-625. doi: 10.2147/DMSO.S237866
[8]	Yu YY, Tong YL, Wu LY, et al. Helicobacter pylori infection eradication for nonalcoholic fatty liver disease: a randomized controlled trial[J]. Sci Rep, 2022, 12: 19530. doi: 10.1038/s41598-022-23746-0
[9]	Chen C, Zhang C, Wang X, et al. Helicobacter pylori infection may increase the severity of nonalcoholic fatty liver disease via promoting liver function damage, glycometabolism, lipid metabolism, inflammatory reaction and metabolic syndrome[J]. Eur J Gastroenterol Hepatol, 2020, 32: 857-866. doi: 10.1097/MEG.0000000000001601
[10]	Wei L, Ding HG. Relationship between Helicobacter pylori infection and nonalcoholic fatty liver disease: What should we expect from a meta-analysis?[J]. Medicine (Baltimore), 2021, 100: e26706. doi: 10.1097/MD.0000000000026706
[11]	Mantovani A, Turino T, Altomari A, et al. Association between Helicobacter pylori infection and risk of nonalcoholic fatty liver disease: An updated meta-analysis[J]. Metabolism, 2019, 96: 56-65. doi: 10.1016/j.metabol.2019.04.012
[12]	Heydari K, Yousefi M, Alizadeh-Navaei R, et al. Helicobacter pylori Infection and Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis[J]. Turk J Gastroenterol, 2022, 33: 171-181. doi: 10.5152/tjg.2022.21467
[13]	Ma Z, Chu X, Yan X, et al. Association between Helicobacter pylori infection and non-alcoholic fatty liver disease for Asian and non-Asian population: A systematic review and meta-analysis[J]. Front Public Health, 2022, 10: 1062942. doi: 10.3389/fpubh.2022.1062942
[14]	Liu R, Liu Q, He Y, et al. Association between Helico-bacter pylori infection and nonalcoholic fatty liver: A meta-analysis[J]. Medicine (Baltimore), 2019, 98: e17781. doi: 10.1097/MD.0000000000017781
[15]	Liu Y, Xu H, Zhao Z, et al. No evidence for a causal link between Helicobacter pylori infection and nonalcoholic fatty liver disease: A bidirectional Mendelian randomization study[J]. Front Microbiol, 2022, 13: 1018322. doi: 10.3389/fmicb.2022.1018322
[16]	Okushin K, Takahashi Y, Yamamichi N, et al. Helicobacter pylori infection is not associated with fatty liver disease including non-alcoholic fatty liver disease: a large-scale cross-sectional study in Japan[J]. BMC Gastroenterol, 2015, 15: 25. doi: 10.1186/s12876-015-0247-9
[17]	Baeg MK, Yoon SK, Ko SH, et al. Helicobacter pylori infection is not associated with nonalcoholic fatty liver disease[J]. World J Gastroenterol, 2016, 22: 2592-2600. doi: 10.3748/wjg.v22.i8.2592
[18]	Wang W, Fan M, Gong R, et al. Helicobacter pylori infection is not an independent risk factor of non-alcoholic fatty liver disease in China[J]. BMC Gastroenterol, 2022, 22: 81. doi: 10.1186/s12876-022-02148-6
[19]	Kazemifar AM, Shafikhani AA, Hajinoormohammadi E, et al. Investigating effect of Helicobacter pylori treatment on improvement of non-alcoholic fatty liver parameters: a randomized trial[J]. Egyptian Liver J, 2019, 9: 2. doi: 10.1186/s43066-019-0001-z
[20]	Sohouli MH, Sayyari AA, Lari A, et al. Association of dietary insulinaemic potential and odds of non-alcoholic fatty liver disease among adults: A case-control study[J]. J Hum Nutr Diet, 2021, 34: 901-909. doi: 10.1111/jhn.12865
[21]	Smith GI, Shankaran M, Yoshino M, et al. Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease[J]. J Clin Invest, 2020, 130: 1453-1460. doi: 10.1172/JCI134165
[22]	Polyzos SA, Kountouras J, Zavos C, et al. The association between Helicobacter pylori infection and insulin resistance: a systematic review[J]. Helicobacter, 2011, 16: 79-88. doi: 10.1111/j.1523-5378.2011.00822.x
[23]	Vafaeimanesh J, Bagherzadeh M, Heidari A, et al. Diabetic patients infected with Helicobacter pylori have a higher Insulin Resistance Degree[J]. Caspian J Intern Med, 2014, 5: 137-142.
[24]	Liou JM, Chen CC, Chang CM, et al. Long-term changes of gut microbiota, antibiotic resistance, and metabolic parameters after Helicobacter pylori eradication: a multicentre, open-label, randomised trial[J]. Lancet Infect Dis, 2019, 19: 1109-1120. doi: 10.1016/S1473-3099(19)30272-5
[25]	Aydemir S, Bayraktaroglu T, Sert M, et al. The effect of Helicobacter pylori on insulin resistance[J]. Dig Dis Sci, 2005, 50: 2090-2093. doi: 10.1007/s10620-005-3012-z
[26]	Azami M, Baradaran HR, Dehghanbanadaki H, et al. Association of Helicobacter pylori infection with the risk of metabolic syndrome and insulin resistance: an updated systematic review and meta-analysis[J]. Diabetol Metab Syndr, 2021, 13: 145. doi: 10.1186/s13098-021-00765-x
[27]	郑凤, 张水英, 孙茂原, 等. 慢性胃炎患者幽门螺旋杆菌感染与IL-6、IL-8和TNF-α的表达研究[J]. 中国初级卫生保健, 2021, 35: 90-91, 94 https://www.cnki.com.cn/Article/CJFDTOTAL-ZGCW202107028.htm
[28]	Kumar V, Kiran S, Kumar S, et al. Extracellular vesicles in obesity and its associated inflammation[J]. Int Rev Immunol, 2022, 41: 30-44. doi: 10.1080/08830185.2021.1964497
[29]	Khan RS, Bril F, Cusi K, et al. Modulation of Insulin Resistance in Nonalcoholic Fatty Liver Disease[J]. Hepatology, 2019, 70: 711-724. doi: 10.1002/hep.30429
[30]	Kakino S, Ohki T, Nakayama H, et al. Pivotal Role of TNF-α in the Development and Progression of Nonalcoholic Fatty Liver Disease in a Murine Model[J]. Horm Metab Res, 2018, 50: 80-87. doi: 10.1055/s-0043-118666
[31]	Leto D, Saltiel AR. Regulation of glucose transport by insulin: traffic control of GLUT4[J]. Nat Rev Mol Cell Biol, 2012, 13: 383-396. doi: 10.1038/nrm3351
[32]	Bian F, Yang XY, Xu G, et al. CRP-Induced NLRP3 Inflammasome Activation Increases LDL Transcytosis Across Endothelial Cells[J]. Front Pharmacol, 2019, 10: 40. doi: 10.3389/fphar.2019.00040
[33]	Fernández-Real JM, Broch M, Vendrell J, et al. Interleukin-6 gene polymorphism and insulin sensitivity[J]. Diabetes, 2000, 49: 517-520. doi: 10.2337/diabetes.49.3.517
[34]	Duan Y, Pan X, Luo J, et al. Association of Inflammatory Cytokines With Non-Alcoholic Fatty Liver Disease[J]. Front Immunol, 2022, 13: 880298. doi: 10.3389/fimmu.2022.880298
[35]	Abdel-Razik A, Mousa N, Shabana W, et al. Helicobacter pylori and non-alcoholic fatty liver disease: A new enigma?[J]. Helicobacter, 2018, 23: e12537.
[36]	Kim YS, Lee SH, Park SG, et al. Low levels of total and high-molecular-weight adiponectin may predict non-alcoholic fatty liver in Korean adults[J]. Metabolism, 2020, 103: 154026. doi: 10.1016/j.metabol.2019.154026
[37]	Mantovani A, Zusi C, Csermely A, et al. Association between lower plasma adiponectin levels and higher liver stiffness in type 2 diabetic individuals with nonalcoholic fatty liver disease: an observational cross-sectional study[J]. Hormones (Athens), 2022, 21: 477-486. doi: 10.1007/s42000-022-00387-6
[38]	Gastaldelli A, Sabatini S, Carli F, et al. PPAR-γ-induced changes in visceral fat and adiponectin levels are associated with improvement of steatohepatitis in patients with NASH[J]. Liver Int, 2021, 41: 2659-2670. doi: 10.1111/liv.15005
[39]	Hemmasi G, Zamani F, Khonsari M, et al. Association between Helicobacter pylori and Serum Leptin in Iranian Dyspeptic Patients[J]. Middle East J Dig Dis, 2013, 5: 158-162.
[40]	Pérez-Pérez A, Sánchez-Jiménez F, Vilariño-García T, et al. Role of Leptin in Inflammation and Vice Versa[J]. Int J Mol Sci, 2020, 21: 5887. doi: 10.3390/ijms21165887
[41]	Shimamoto T, Yamamichi N, Gondo K, et al. The association of Helicobacter pylori infection with serum lipid profiles: An evaluation based on a combination of meta-analysis and a propensity score-based observational approach[J]. PLoS One, 2020, 15: e0234433. doi: 10.1371/journal.pone.0234433
[42]	Park Y, Kim TJ, Lee H, et al. Eradication of Helicobacter pylori infection decreases risk for dyslipidemia: A cohort study[J]. Helicobacter, 2021, 26: e12783.
[43]	Eshraghian A, Nikeghbalian S, Shamsaeefar A, et al. Hepatic steatosis and liver fat contents in liver transplant recipients are associated with serum adipokines and insulin resistance[J]. Sci Rep, 2020, 10: 12701. doi: 10.1038/s41598-020-69571-1
[44]	Stefan N, Häring HU. The role of hepatokines in metabolism[J]. Nat Rev Endocrinol, 2013, 9: 144-152. doi: 10.1038/nrendo.2012.258
[45]	Hennige AM, Staiger H, Wicke C, et al. Fetuin-A induces cytokine expression and suppresses adiponectin production[J]. PLoS One, 2008, 3: e1765. doi: 10.1371/journal.pone.0001765
[46]	Shim YS, Kang MJ, Oh YJ, et al. Fetuin-A as an Alternative Marker for Insulin Resistance and Cardiovascular Risk in Prepubertal Children[J]. J Atheroscler Thromb, 2017, 24: 1031-1038. doi: 10.5551/jat.38323
[47]	Jirak P, Stechemesser L, Moré E, et al. Clinical implications of fetuin-A[J]. Adv Clin Chem, 2019, 89: 79-130.
[48]	Pal D, Dasgupta S, Kundu R, et al. Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance[J]. Nat Med, 2012, 18: 1279-1285. doi: 10.1038/nm.2851
[49]	Filardi T, Panimolle F, Tiberti C, et al. Circulating levels of fetuin-A are associated with moderate-severe hepatic steatosis in young adults[J]. J Endocrinol Invest, 2021, 44: 105-110. doi: 10.1007/s40618-020-01274-w
[50]	Chen LW, Kuo SF, Chen CH, et al. A community-based study on the association between Helicobacter pylori Infection and obesity[J]. Sci Rep, 2018, 8: 10746. doi: 10.1038/s41598-018-28792-1
[51]	Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents[J]. Nat Rev Mol Cell Biol, 2020, 21: 363-383. doi: 10.1038/s41580-020-0230-3
[52]	Arroyave-Ospina JC, Wu Z, Geng Y, et al. Role of Oxidative Stress in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Implications for Prevention and Therapy[J]. Antioxidants (Basel), 2021, 10: 174. doi: 10.3390/antiox10020174
[53]	Sun X, Seidman JS, Zhao P, et al. Neutralization of Oxidized Phospholipids Ameliorates Non-alcoholic Steatohepatitis[J]. Cell Metab, 2020, 31: 189-206. e8. doi: 10.1016/j.cmet.2019.10.014
[54]	Shepard CR. TLR9 in MAFLD and NASH: At the Intersection of Inflammation and Metabolism[J]. Front Endocrinol (Lausanne), 2020, 11: 613639.
[55]	Ding SZ, Minohara Y, Fan XJ, et al. Helicobacter pylori infection induces oxidative stress and programmed cell death in human gastric epithelial cells[J]. Infect Immun, 2007, 75: 4030-4039. doi: 10.1128/IAI.00172-07
[56]	Handa O, Naito Y, Yoshikawa T. Helicobacter pylori: a ROS-inducing bacterial species in the stomach[J]. Inflamm Res, 2010, 59: 997-1003. doi: 10.1007/s00011-010-0245-x
[57]	Oh JH, Lee JH, Cho MS, et al. Characterization of Gut Microbiome in Korean Patients with Metabolic Associated Fatty Liver Disease[J]. Nutrients, 2021, 13: 1013. doi: 10.3390/nu13031013
[58]	Craven L, Rahman A, Nair Parvathy S, et al. Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial[J]. Am J Gastroenterol, 2020, 115: 1055-1065. doi: 10.14309/ajg.0000000000000661
[59]	Aron-Wisnewsky J, Vigliotti C, Witjes J, et al. Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders[J]. Nat Rev Gastroenterol Hepatol, 2020, 17: 279-297. doi: 10.1038/s41575-020-0269-9
[60]	Heimesaat MM, Fischer A, Plickert R, et al. Helicobacter pylori induced gastric immunopathology is associated with distinct microbiota changes in the large intestines of long-term infected Mongolian gerbils[J]. PLoS One, 2014, 9: e100362. doi: 10.1371/journal.pone.0100362
[61]	He C, Peng C, Xu X, et al. Probiotics mitigate Helico-bacter pylori-induced gastric inflammation and premalignant lesions in INS-GAS mice with the modulation of gastrointestinal microbiota[J]. Helicobacter, 2022, 27: e12898.
[62]	Cheng DD, He C, Ai HH, et al. The Possible Role of Helicobacter pylori Infection in Non-alcoholic Fatty Liver Disease[J]. Front Microbiol, 2017, 8: 743. doi: 10.3389/fmicb.2017.00743
[63]	Doulberis M, Papaefthymiou A, Srivastava DS, et al. Update on the association between non-alcoholic fatty liver disease and Helicobacter pylori infection[J]. Int J Clin Pract, 2021, 75: e13737.
[64]	Zhang C, Guo L, Qin Y, et al. Correlation between Helicobacter pylori infection and polymorphism of adiponectin gene promoter-11391G/A, superoxide dismutase gene in nonalcoholic fatty liver disease[J]. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2016, 41: 359-366.
[65]	张超贤, 郭李柯, 张利利, 等. 幽门螺杆菌感染与PPARγ2基因Pro12Ala、GPx-1基因Pro198Leu多态性的交互作用和非酒精性脂肪性肝病的关系[J]. 临床肝胆病杂志, 2019, 35: 1551-1559. https://www.cnki.com.cn/Article/CJFDTOTAL-LCGD201907032.htm
[66]	方德周, 方彦旭, 贾星星. HP感染后Men1基因对非酒精性脂肪肝病及炎症反应的调控机制[J]. 基因组学与应用生物学, 2020, 39: 1824-1829. https://www.cnki.com.cn/Article/CJFDTOTAL-GXNB202004048.htm
[67]	Eslam M, Newsome PN, Sarin SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement[J]. J Hepatol, 2020, 73: 202-209. doi: 10.1016/j.jhep.2020.03.039

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幽门螺杆菌感染与非酒精性脂肪性肝病的相关性及潜在机制

doi: 10.12290/xhyxzz.2022-0710

通讯作者:
任茜, E-mail: ldyy_renqian@lzu.edu.cn

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Relationship and Potential Mechanism Between Helicobacter Pylori Infection and Non-alcoholic Fatty Liver Disease

Corresponding author: REN Qian, E-mail: ldyy_renqian@lzu.edu.cn

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幽门螺杆菌感染与非酒精性脂肪性肝病的相关性及潜在机制

doi: 10.12290/xhyxzz.2022-0710

通讯作者: 任茜, E-mail: ldyy_renqian@lzu.edu.cn

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Relationship and Potential Mechanism Between Helicobacter Pylori Infection and Non-alcoholic Fatty Liver Disease

Corresponding author: REN Qian, E-mail: ldyy_renqian@lzu.edu.cn

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通讯作者:
任茜, E-mail: ldyy_renqian@lzu.edu.cn