肠道菌群在自身免疫性疾病治疗中的前景

赵丽丹; 孟夏; 徐浩杰; 张奉春

doi:10.12290/xhyxzz.2022-0245

肠道菌群在自身免疫性疾病治疗中的前景

doi: 10.12290/xhyxzz.2022-0245

中国医学科学院北京协和医院风湿免疫科国家皮肤与免疫疾病临床医学研究中心教育部重点实验室, 北京 100730

基金项目:

国家自然科学基金（ 82071840）；中国医学科学院医学与健康科技创新工程项目（ CIFMS2020-I2M-C&T-B-013）

详细信息

通讯作者:
张奉春,E-mail:zhangfccra@aliyun.com

中图分类号: R378;R593
计量
- 文章访问数: 5
- HTML全文浏览量: 0
- PDF下载量: 2
- 被引次数: 0
出版历程
- 收稿日期: 2022-05-02
- 录用日期: 2022-07-15
- 网络出版日期: 2022-07-28

Prospect of Gut Microbiota Based Intervention in Autoimmune Disease Control

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Education Key Laboratory, Beijing 100730, China

Funds:

National Natural Science Foundation of China (82071840), CAMS Innovation Fund for Medical Sciences (CIFMS 2020-I2M-C&T-B-013)

摘要

摘要: 肠道菌群对于维持人体免疫稳态不可或缺。肠道菌群失调、易位及菌群代谢物异常见于多种自身免疫性疾病，通过诱导免疫失衡、分子模拟、旁观者激活、表位扩展等机制参与自身免疫耐受破坏和过度炎症反应，促进自身免疫性疾病的发生发展，并通过干扰药物在肠道的转化影响免疫治疗药物的疗效和毒性。基于肠道菌群的干预措施或可为自身免疫性疾病的防治提供新策略。本文回顾近年来肠道菌群在系统性自身免疫性疾病中的研究进展，并对基于菌群的干预措施在自身免疫性疾病中的应用前景予以展望。
- 肠道菌群 /
- 自身免疫性疾病 /
- 菌群干预
Abstract: Gut microbiota is recognized of its indispensability for the maintenance of human immune homeostasis. Dysbiosis and translocation of gut microbes as well as aberrance of microbiome metabolites have been revealed in many autoimmune diseases, which participate in the breakdown of immune tolerance and excessive inflammatory responses. The involved mechanisms include skewing immune equilibrium, molecular mimicry, bystander activation and epitope spreading which integrate and contribute to the initiation and progression of autoimmune diseases. In addition, the microbial biotransformation of antirheumatic drugs help determine the bioactivity and toxicity of these drugs. Herein, gut microbiota-based intervention may shed light on developing novel strategies for prophylaxis and treatment of autoimmune diseases. In this review, recent advances in exploring the potential pathogenic role of gut microbiota in autoimmunity were summarized and the prospect of applying microbiota-based intervention in systemic autoimmune diseases was addressed.
- gut microbiota /
- autoimmune disease /
- microbiota-based intervention

HTML全文

参考文献(60)

[1]	Hevia A, Milani C, Lopez P, et al. Intestinal dysbiosis associated with systemic lupus erythematosus[J]. mBio, 2014, 5:e01548-14.
[2]	He Z,Shao T, Li H, et al. Alterations of the gut microbiome in Chinese patients with systemic lupus erythematosus[J].Gut Pathog, 2016, 8:64.
[3]	Chen BD, Jia XM, Xu JY, et al. An Autoimmunogenic and Proinflammatory Profile Defined by the Gut Microbiota of Patients With Untreated Systemic Lupus Erythematosus[J]. Arthritis Rheumatol, 2021, 73:232-243.
[4]	Azzouz D, Omarbekova A, Heguy A, et al. Lupus nephritis is linked to diseaseactivity associated expansions and immunity to a gut commensal[J]. Ann Rheum Dis, 2019, 78:947-956.
[5]	Scher JU, Sczesnak A, Longman RS, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis[J]. Elife, 2013, 2:e01202.
[6]	Zhang X, Zhang D, Jia H, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment[J]. Nat Med, 2015, 21:895-905.
[7]	Tang R, Wei Y, Li Y, et al. Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy[J]. Gut, 2018, 67:534-541.
[8]	Breban M, Tap J, Leboime A, et al. Faecal microbiota study reveals specific dysbiosis in spondyloarthritis[J]. Ann Rheum Dis, 2017, 76:1614-1622.
[9]	Mandl T, Marsal J, Olsson P, et al. Severe intestinal dysbiosis is prevalent in primary Sjogren's syndrome and is associated with systemic disease activity[J]. Arthritis Res Ther, 2017, 19:237.
[10]	Cano-Ortiz A, Laborda-Illanes A, Plaza-Andrades I, et al. Connection between the Gut Microbiome, Systemic Inflammation, Gut Permeability and FOXP3 Expression in Patients with Primary Sjogren's Syndrome[J]. Int J Mol Sci, 2020, 21:8733.
[11]	Zhou C, Zhao H, Xiao XY, et al. Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis[J]. J Autoimmun, 2020, 107:102360.
[12]	Breban M, Tap J, Leboime A, et al. Faecal microbiota study reveals specific dysbiosis in spondyloarthritis[J]. Ann Rheum Dis, 2017, 76:1614-1622.
[13]	Hall AB, Yassour M, Sauk J, et al. A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients[J]. Genome Med, 2017, 9:103.
[14]	Gomez-Banuelos E, Mukherjee A, Darrah E, et al. Rheumatoid ArthritisAssociated Mechanisms of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans[J]. J Clin Med, 2019, 8:1309.
[15]	Bagavant H, Dunkleberger ML, Wolska N, et al. Antibodies to periodontogenic bacteria are associated with higher disease activity in lupus patients[J]. Clin Exp Rheumatol, 2019, 37:106-111.
[16]	Manfredo Vieira S, Hiltensperger M, Kumar V, et al. Translocation of a gut pathobiont drives autoimmunity in mice and humans[J]. Science, 2018, 359:1156-1161.
[17]	Zegarra-Ruiz DF, El Beidaq A, Iniguez AJ, et al. A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity[J]. Cell Host Microbe, 2019, 25:113-127. e6.
[18]	Ruff WE, Dehner C, Kim WJ, et al. Pathogenic Autoreactive T and B Cells CrossReact with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity[J]. Cell Host Microbe, 2019, 26:100-113. e8.
[19]	Greiling TM, Dehner C, Chen X, et al. Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus[J]. Sci Transl Med, 2018, 10:eaan2306.
[20]	Szymula A, Rosenthal J, Szczerba BM, et al. T cell epitope mimicry between Sjogren's syndrome Antigen A (SSA)/Ro60 and oral, gut, skin and vaginal bacteria[J]. Clin Immunol, 2014, 152:1-9.
[21]	Zhang L, Zhang YJ, Chen J, et al. The association of HLA-B27 and Klebsiella pneumoniae in ankylosing spondylitis:A systematic review[J]. Microb Pathog, 2018, 117:49-54.
[22]	Furusawa Y, Obata Y, Fukuda S, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells[J]. Nature, 2013, 504:446-50.
[23]	Sivaprakasam S, Prasad PD, Singh N. Benefits of Short-chain fatty acids and their receptors in inflammation and carcinogenesis[J]. Pharmacol Ther, 2016, 164:144-151.
[24]	Rosser EC, Piper CJM, Matei DE, et al. Microbiota-Derived Metabolites Suppress Arthritis by Amplifying Aryl-Hydrocarbon Receptor Activation in Regulatory B Cells[J]. Cell Metab, 2020, 31:837-851,e10.
[25]	Sanchez HN, Moroney JB, Gan H, et al. B cell-intrinsic epigenetic modulation of antibody responses by dietary fiber-derived short-chain fatty acids[J]. Nat Commun, 2020, 11:60.
[26]	Kidd BA, Ho PP, Sharpe O, et al. Epitope spreading to citrullinated antigens in mouse models of autoimmune arthritis and demyelination[J]. Arthritis Res Ther, 2008, 10:R119.
[27]	Bagavant H, Araszkiewicz AM, Ingram JK, et al. Immune Response to Enterococcus gallinarum in Lupus Patients Is Associated With a Subset of Lupus-Associated Autoantibodies[J]. Front Immunol, 2021, 12:635072.
[28]	Hsu TC, Huang CY, Liu CH, et al. Lactobacillus paracasei GMNL-32, Lactobacillus reuteri GMNL-89 and L. reuteri GMNL-263 ameliorate hepatic injuries in lupusprone mice[J]. Br J Nutr, 2017, 117:1066-1074.
[29]	Yeh YL, Lu MC, Tsai BC, et al. Heat-Killed Lactobacillus reuteri GMNL-263 Inhibits Systemic Lupus Erythematosus-Induced Cardiomyopathy in NZB/W F1 Mice[J]. Probiotics Antimicrob Proteins, 2021, 13:51-59.
[30]	Tzang BS, Liu CH, Hsu KC, et al. Effects of oral Lactobacillus administration on antioxidant activities and CD4+CD25+forkhead box P3(FoxP3)+T cells in NZB/W F1 mice[J]. Br J Nutr, 2017, 118:333-342.
[31]	Li Y, Wang HF, Li X, et al. Disordered intestinal microbes are associated with the activity of Systemic Lupus Erythematosus[J]. Clin Sci (Lond), 2019, 133:821-838.
[32]	Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors[J]. Science, 2018, 359:91-97.
[33]	Artacho A, Isaac S, Nayak R, et al. The Pretreatment Gut Microbiome Is Associated With Lack of Response to Methotrexate in New-Onset Rheumatoid Arthritis[J]. Arthritis Rheumatol, 2021, 73:931-942.
[34]	Nayak RR, Alexander M, Deshpande I, et al. Methotrexate impacts conserved pathways in diverse human gut bacteria leading to decreased host immune activation[J]. Cell Host Microbe, 2021, 29:362-377,e11.
[35]	Zaragoza-Garcia O, Castro-Alarcon N, Perez-Rubio G, et al. DMARDs-Gut Microbiota Feedback:Implications in the Response to Therapy[J]. Biomolecules, 2020, 10:1479.
[36]	Araya RE, Goldszmid RS. Two Bugs a NOD Away from Improving Cancer Therapy Efficacy[J]. Immunity, 2016, 45:714-716.
[37]	Chen J, Wright K, Davis JM, et al. An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis[J]. Genome Med, 2016, 8:43.
[38]	Flannigan KL, Taylor MR, Pereira SK, et al. An intact microbiota is required for the gastrointestinal toxicity of the immunosuppressant mycophenolate mofetil[J]. J Heart Lung Transplant, 2018, 37:1047-1059.
[39]	Taylor MR, Flannigan KL, Rahim H, et al. Vancomycin relieves mycophenolate mofetil-induced gastrointestinal toxicity by eliminating gut bacterial betaglucuronidase activity[J]. Sci Adv, 2019, 5:eaax2358.
[40]	Kim DS, Park Y, Choi JW, et al. Lactobacillus acidophilus Supplementation Exerts a Synergistic Effect on Tacrolimus Efficacy by Modulating Th17/Treg Balance in Lupus-Prone Mice via the SIGNR3 Pathway[J]. Front Immunol, 2021, 12:696074.
[41]	Furukawa M, Moriya K, Nakayama J, et al. Gut dysbiosis associated with clinical prognosis of patients with primary biliary cholangitis[J]. Hepatol Res, 2020, 50:840-852.
[42]	Bazin T, Hooks KB, Barnetche T, et al. Microbiota Composition May Predict AntiTnf Alpha Response in Spondyloarthritis Patients:an Exploratory Study[J]. Sci Rep, 2018, 8:5446.
[43]	Yin J, Sternes PR, Wang M, et al. Shotgun metagenomics reveals an enrichment of potentially cross-reactive bacterial epitopes in ankylosing spondylitis patients, as well as the effects of TNFi therapy upon microbiome composition[J]. Ann Rheum Dis, 2020, 79:132-140.
[44]	Zhou Y, Xu ZZ, He Y, et al. Gut Microbiota Offers Universal Biomarkers across Ethnicity in Inflammatory Bowel Disease Diagnosis and Infliximab Response Prediction[J]. mSystems, 2018, 3 e00188-17.
[45]	Aden K, Rehman A, Waschina S, et al. Metabolic Functions of Gut Microbes Associate With Efficacy of Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Diseases[J]. Gastroenterology, 2019, 157:1279-1292. e11.
[46]	Pan H, Guo R, Ju Y, et al. A single bacterium restores the microbiome dysbiosis to protect bones from destruction in a rat model of rheumatoid arthritis[J]. Microbiome, 2019, 7:107.
[47]	Zamani B, Golkar HR, Farshbaf S, et al. Clinical and metabolic response to probiotic supplementation in patients with rheumatoid arthritis:a randomized, double-blind, placebo-controlled trial[J]. Int J Rheum Dis, 2016, 19:869-879.
[48]	Alpizar-Rodriguez D, Lesker TR, Gronow A, et al. Prevotella copri in individuals at risk for rheumatoid arthritis[J]. Ann Rheum Dis, 2019, 78:590-593.
[49]	Marietta EV, Murray JA, Luckey DH, et al. Suppression of Inflammatory Arthritis by Human Gut-Derived Prevotella histicola in Humanized Mice[J]. Arthritis Rheumatol, 2016, 68:2878-2888.
[50]	Mandel DR, Eichas K, Holmes J. Bacillus coagulans:a viable adjunct therapy for relieving symptoms of rheumatoid arthritis according to a randomized, controlled trial.[J] BMC Complement Altern Med, 2010, 10:1.
[51]	Shokryazdan P, Faseleh Jahromi M, Navidshad B, et al. Effects of prebiotics on immune system and cytokine expression[J]. Med Microbiol Immunol, 2017, 206:1-9.
[52]	Wilson B, Eyice O, Koumoutsos I, et al. Prebiotic Galactooligosaccharide Supplementation in Adults with Ulcerative Colitis:Exploring the Impact on Peripheral Blood Gene Expression, Gut Microbiota, and Clinical Symptoms[J]. Nutrients, 2021, 13:3598.
[53]	Ho J, Nicolucci AC, Virtanen H, et al. Effect of Prebiotic on Microbiota, Intestinal Permeability, and Glycemic Control in Children With Type 1 Diabetes[J]. J Clin Endocrinol Metab, 2019, 104:4427-4440.
[54]	Moro G, Arslanoglu S, Stahl B, et al. A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age[J]. Arch Dis Child, 2006, 91:814-819.
[55]	Zeng J, Peng L, Zheng W, et al. Fecal microbiota transplantation for rheumatoid arthritis:A case report[J]. Clin Case Rep, 2020, 9:906-909.
[56]	Kragsnaes MS, Kjeldsen J, Horn HC,et al. Efficacy and safety of faecal microbiota transplantation in patients with psoriatic arthritis:protocol for a 6-month, doubleblind, randomised, placebo-controlled trial[J]. BMJ Open, 2018, 8:e019231.
[57]	Picchianti Diamanti A, Panebianco C, Salerno G, et al. Impact of Mediterranean Diet on Disease Activity and Gut Microbiota Composition of Rheumatoid Arthritis Patients.[J] Microorganisms, 2020, 8:1989.
[58]	Gutierrez-Diaz I, Fernandez-Navarro T, Sanchez B, et al. Mediterranean diet and faecal microbiota:a transversal study[J]. Food Funct, 2016, 7:2347-2356.
[59]	Wilck N, Matus MG, Kearney SM, et al. Salt-responsive gut commensal modulates TH17 axis and disease[J]. Nature, 2017, 551:585-589.
[60]	Zhang H, Liao X, Sparks JB, et al. Dynamics of gut microbiota in autoimmune lupus[J]. Appl Environ Microbiol, 2014, 80:7551-7560.

施引文献

资源附件(0)

访问统计

点击查看大图

计量

文章访问数: 5
HTML全文浏览量: 0
PDF下载量: 2
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

地址：	北京市东城区帅府园1号北京协和医院老楼7号楼 3层302室《协和医学杂志》编辑部
电话：	010-69154261/4262
E - mail：	medj@pumch.cn mjpumch@126.com
期刊网站版权所有：	《协和医学杂志》编辑部京ICP备 11002662

留言板

肠道菌群在自身免疫性疾病治疗中的前景

doi: 10.12290/xhyxzz.2022-0245

通讯作者:
张奉春,E-mail:zhangfccra@aliyun.com

计量

Prospect of Gut Microbiota Based Intervention in Autoimmune Disease Control

计量

目录

留言板

肠道菌群在自身免疫性疾病治疗中的前景

doi: 10.12290/xhyxzz.2022-0245

通讯作者: 张奉春,E-mail:zhangfccra@aliyun.com

计量

出版历程

Prospect of Gut Microbiota Based Intervention in Autoimmune Disease Control

计量

出版历程

目录

通讯作者:
张奉春,E-mail:zhangfccra@aliyun.com