山东大学耳鼻喉眼学报 ›› 2022, Vol. 36 ›› Issue (3): 116-122.doi: 10.6040/j.issn.1673-3770.0.2021.496

• 研究进展 • 上一篇    下一篇

肠道微生态在儿童变应性鼻炎中的研究现状

林一杭,李幼瑾   

  1. 上海交通大学医学院附属上海儿童医学中心 耳鼻咽喉科, 上海 200127
  • 发布日期:2022-06-15
  • 通讯作者: 李幼瑾. E-mail:kevinliyoujin@163.com
  • 基金资助:
    国家自然科学基金面上项目(82071015);上海市科学技术委员会“科技创新行动计划”医学创新研究专项项目(21Y11900200)

Research progress on gut microbiome in children with allergic rhinitis

LIN YihangOverview,LI Youjin   

  1. Department of Otorhinolaryngology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
  • Published:2022-06-15

摘要: 随着对肠道微生态结构与功能研究的不断深入,肠道菌群与变应性疾病的发生、发展与病情转归的联系被证实。在儿童的生长发育过程中,肠道内各种菌群不断发生动态演变,不同年龄阶段肠道微生态的不同特征及其与变应性鼻炎(AR)之间都有其相对应的互动关系。AR作为最为常见的儿童慢性呼吸道疾病之一,针对其治疗的临床药物种类有限,而免疫治疗方式疗程长被接受度低。除以上两种主要治疗模式外,目前已有学者开展了以探究调整肠道微生态对AR儿童进行干预的有效收益评估的临床研究。综述对儿童群体中与AR相关的肠道微生物群临床研究与干预进展进行整理总结,以期评估肠道微生物群在AR发生、治疗方面的相关理论与机制的应用价值。

关键词: 肠道微生态, 变应性鼻炎, 粪菌移植, 儿童

Abstract: With increasing awareness of the specialization of the structure and function of microbiota, the relationship between gut microbiota and the occurrence, development, and outcome of allergic diseases has been explored. The development of gut microbiota during childhood is a highly dynamic process and the characteristics of gut microbiota in children of different ages closely correlate with allergic rhinitis(AR). Although AR is the most common chronic respiratory disease in children, it currently has poor clinical outcomes with drug treatment and low acceptability of long-term immunotherapy treatment. Numerous clinical studies have been conducted to explore the benefits of adjusting the gut microbiota in children with AR. This review summarizes the progress in the clinical research of gut microbiota and potential interventions and evaluates the feasibility of fecal microbiota transplantation in treating allergic diseases.

Key words: Gut microbiome, Allergic rhinitis, Fecal microbiota transplantation, Pediatric

中图分类号: 

  • R765.21
[1] Mastrorilli C, Posa D, Cipriani F, et al. Asthma and allergic rhinitis in childhood: what's new[J]. Pediatr Allergy Immunol, 2016, 27(8): 795-803. doi:10.1111/pai.12681.
[2] 向莉, 申昆玲. 儿童常见过敏性疾病诊疗概述[J]. 中国医学前沿杂志(电子版), 2013, 5(8): 1-5. doi:10.3969/j.issn.1674-7372.2013.08.001.
[3] Zhang Y, Zhang L. Increasing prevalence of allergic rhinitis in China[J]. Allergy Asthma Immunol Res, 2019, 11(2): 156-169. doi:10.4168/aair.2019.11.2.156.
[4] Hassan A, Blanchard N. Microbial(co)infections: powerful immune influencers[J]. PLoS Pathog, 2022, 18(2): e1010212. doi:10.1371/journal.ppat.1010212.
[5] Shen X, Wang ML, Zhang X, et al. Dynamic construction of gut microbiota may influence allergic diseases of infants in Southwest China[J]. BMC Microbiol, 2019, 19(1): 123. doi:10.1186/s12866-019-1489-4.
[6] Johnson CC, Ownby DR. The infant gut bacterial microbiota and risk of pediatric asthma and allergic diseases[J]. Transl Res, 2017, 179: 60-70. doi:10.1016/j.trsl.2016.06.010.
[7] Shi N, Li N, Duan XW, et al. Interaction between the gut microbiome and mucosal immune system[J]. Mil Med Res, 2017, 4: 14. doi:10.1186/s40779-017-0122-9.
[8] Milani C, Duranti S, Bottacini F, et al. The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota[J]. Microbiol Mol Biol Rev, 2017, 81(4): e00036-e00017. doi:10.1128/MMBR.00036-17.
[9] Akagawa S, Kaneko K. Gut microbiota and allergic diseases in children[J]. Allergol Int, 2022, 18: S1323-S8930(22)00012-0. doi:10.1016/j.alit.2022.02.004.
[10] Melli LC, do Carmo-Rodrigues MS, Araújo-Filho HB, et al. Intestinal microbiota and allergic diseases: a systematic review[J]. Allergol Immunopathol(Madr), 2016, 44(2): 177-188. doi:10.1016/j.aller.2015.01.013.
[11] 梁峥琰, 邓玉琴, 陶泽璋. 母亲过敏和环境暴露对免疫成熟的影响[J]. 山东大学耳鼻喉眼学报, 2018, 32(3): 96-104. doi:10.6040/j.issn.1673-3770.0.2017.363. LIANG Zhengyan, DENG Yuqin, TAO Zezhang. Effect of maternal allergy and environmental exposure on immune maturation[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2018, 32(3): 96-104.doi:10.6040/j.issn.1673-3770.0.2017.363.
[12] Venter C, Agostoni C, Arshad SH, et al. Dietary factors during pregnancy and atopic outcomes in childhood: a systematic review from the european academy of allergy and clinical immunology[J]. Pediatr Allergy Immunol, 2020, 31(8): 889-912. doi:10.1111/pai.13303.
[13] Bertelsen RJ, Brantsæter AL, Magnus MC, et al. Probiotic milk consumption in pregnancy and infancy and subsequent childhood allergic diseases[J]. J Allergy Clin Immunol, 2014, 133(1): 165-171.e1-8. doi:10.1016/j.jaci.2013.07.032.
[14] Kristensen K, Henriksen L. Cesarean section and disease associated with immune function[J]. J Allergy Clin Immunol, 2016, 137(2): 587-590. doi:10.1016/j.jaci.2015.07.040.
[15] Dominguez-Bello MG, Costello EK, Contreras M, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns[J]. Proc Natl Acad Sci USA, 2010, 107(26): 11971-11975. doi:10.1073/pnas.1002601107.
[16] Kuo CH, Kuo HF, Huang CH, et al. Early life exposure to antibiotics and the risk of childhood allergic diseases: an update from the perspective of the hygiene hypothesis[J]. Wei Mian Yu Gan Ran Za Zhi, 2013, 46(5): 320-329. doi:10.1016/j.jmii.2013.04.005.
[17] Mitre E, Susi A, Kropp LE, et al. Association between use of acid-suppressive medications and antibiotics during infancy and allergic diseases in early childhood[J]. JAMA Pediatr, 2018, 172(6): e180315. doi:10.1001/jamapediatrics.2018.0315.
[18] González-Díaz SN, Del Río-Navarro BE, Pietropaolo-Cienfuegos DR, et al. Factors associated with allergic rhinitis in children and adolescents from northern Mexico: International Study of Asthma and Allergies in Childhood Phase IIIB [J]. Allergy Asthma Proc, 2010, 31(4): e53-e62. doi:10.2500/aap.2010.31.3346.
[19] Chiu CY, Chan YL, Tsai MH, et al. Gut microbial dysbiosis is associated with allergen-specific IgE responses in young children with airway allergies[J]. World Allergy Organ J, 2019, 12(3): 100021. doi:10.1016/j.waojou.2019.100021.
[20] Michaudel C, Sokol H. The gut microbiota at the service of immunometabolism[J]. Cell Metab, 2020, 32(4): 514-523. doi:10.1016/j.cmet.2020.09.004.
[21] Kemter AM, Nagler CR. Influences on allergic mechanisms through gut, lung, and skin microbiome exposures[J]. J Clin Invest, 2019, 129(4): 1483-1492. doi:10.1172/JCI124610.
[22] Simonyté Sjödin K, Hammarström ML, Rydén P, et al. Temporal and long-term gut microbiota variation in allergic disease: a prospective study from infancy to school age[J]. Allergy, 2019, 74(1): 176-185. doi:10.1111/all.13485.
[23] Arrieta MC, Arévalo A, Stiemsma L, et al. Associations between infant fungal and bacterial dysbiosis and childhood atopic wheeze in a nonindustrialized setting[J]. J Allergy Clin Immunol, 2018, 142(2): 424-434.e10. doi:10.1016/j.jaci.2017.08.041.
[24] Stokholm J, Blaser MJ, Thorsen J, et al. Maturation of the gut microbiome and risk of asthma in childhood[J]. Nat Commun, 2018, 9(1): 141. doi:10.1038/s41467-017-02573-2.
[25] Singh N, Gurav A, Sivaprakasam S, et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis[J]. Immunity, 2014, 40(1): 128-139. doi:10.1016/j.immuni.2013.12.007.
[26] Arpaia N, Campbell C, Fan XY, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation[J]. Nature, 2013, 504(7480): 451-455. doi:10.1038/nature12726.
[27] Byndloss MX, Olsan EE, Rivera-Chávez F, et al. Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion[J]. Science, 2017, 357(6351): 570-575. doi:10.1126/science.aam9949.
[28] McKenzie C, Tan J, Macia L, et al. The nutrition-gut microbiome-physiology axis and allergic diseases[J]. Immunol Rev, 2017, 278(1): 277-295. doi:10.1111/imr.12556.
[29] Magnúsdóttir S, Ravcheev D, de Crécy-Lagard V, et al. Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes[J]. Front Genet, 2015, 6: 148. doi:10.3389/fgene.2015.00148.
[30] Chiu CY, Cheng ML, Chiang MH, et al. Gut microbial-derived butyrate is inversely associated with IgE responses to allergens in childhood asthma[J]. Pediatr Allergy Immunol, 2019, 30(7): 689-697. doi:10.1111/pai.13096.
[31] Zimmermann P, Messina N, Mohn WW, et al. Association between the intestinal microbiota and allergic sensitization, eczema, and asthma: a systematic review[J]. J Allergy Clin Immunol, 2019, 143(2): 467-485. doi:10.1016/j.jaci.2018.09.025.
[32] Underhill DM, Iliev ID. The mycobiota: interactions between commensal fungi and the host immune system[J]. Nat Rev Immunol, 2014, 14(6): 405-416. doi:10.1038/nri3684.
[33] Schei K, Simpson MR, Øien T, et al. Allergy-related diseases and early gut fungal and bacterial microbiota abundances in children[J]. Clin Transl Allergy, 2021, 11(5): e12041. doi:10.1002/clt2.12041.
[34] 林一杭, 芮晓清, 李幼瑾. 肠道菌群在血清tIgE水平升高的变应性鼻炎儿童发病中的作用[J]. 临床耳鼻咽喉头颈外科杂志, 2020, 34(12): 1123-1128. doi:10.13201/j.issn.2096-7993.2020.12.016. LIN Yihang, RUI Xiaoqing, LI Youjin. Role of gut microbiota in children with allergic rhinitis with high serum total IgE level[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2020, 34(12): 1123-1128. doi:10.13201/j.issn.2096-7993.2020.12.016.
[35] Chua HH, Chou HC, Tung YL, et al. Intestinal dysbiosis featuring abundance of Ruminococcus gnavus associates with allergic diseases in infants[J]. Gastroenterology, 2018, 154(1): 154-167. doi:10.1053/j.gastro.2017.09.006.
[36] Su YJ, Luo SD, Hsu CY, et al. Differences in gut microbiota between allergic rhinitis, atopic dermatitis, and skin urticaria: a pilot study[J]. Medicine(Baltimore), 2021, 100(9): e25091. doi:10.1097/MD.0000000000025091.
[37] Kukkonen K, Savilahti E, Haahtela T, et al. Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial[J]. J Allergy Clin Immunol, 2007, 119(1): 192-198. doi:10.1016/j.jaci.2006.09.009.
[38] Zajac AE, Adams AS, Turner JH. A systematic review and meta-analysis of probiotics for the treatment of allergic rhinitis[J]. Int Forum Allergy Rhinol, 2015, 5(6): 524-532. doi:10.1002/alr.21492.
[39] Huang JL, Zhang J, Wang XZ, et al. Effect of probiotics on respiratory tract allergic disease and gut microbiota[J]. Front Nutr, 2022, 9: 821900. doi:10.3389/fnut.2022.821900.
[40] Blackwood BP, Yuan CY, Wood DR, et al. Probiotic Lactobacillus species strengthen intestinal barrier function and tight junction integrity in experimental necrotizing enterocolitis[J]. J Probiotics Health, 2017, 5(1): 159. doi:10.4172/2329-8901.1000159.
[41] Secher T, Maillet I, Mackowiak C, et al. The probiotic strain Escherichia coli Nissle 1917 prevents papain-induced respiratory barrier injury and severe allergic inflammation in mice[J]. Sci Rep, 2018, 8(1): 11245. doi:10.1038/s41598-018-29689-9.
[42] Chen Y, Zhang M, Ren FZ. A role of exopolysaccharide produced by Streptococcus thermophilus in the intestinal inflammation and mucosal barrier in caco-2 monolayer and dextran sulphate sodium-induced experimental murine colitis[J]. Molecules, 2019, 24(3): 513. doi:10.3390/molecules24030513.
[43] Dennis-Wall JC, Culpepper T, Nieves C Jr, et al. Probiotics(Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2)improve rhinoconjunctivitis-specific quality of life in individuals with seasonal allergies: a double-blind, placebo-controlled, randomized trial[J]. Am J Clin Nutr, 2017, 105(3): 758-767. doi:10.3945/ajcn.116.140012.
[44] Lee DH, Park HK, Lee HR, et al. Immunoregulatory effects of Lactococcus lactis-derived extracellular vesicles in allergic asthma[J]. Clin Transl Allergy, 2022, 12(3): e12138. doi:10.1002/clt2.12138.
[45] 孙中美, 李军祥, 胡立明, 等. 葛洪《肘后备急方》应用粪便治疗疾病探析[J]. 中医学报, 2019, 34(5): 916-919. doi:10.16368/j.issn.1674-8999.2019.05.218. SUN Zhongmei, LI Junxiang, HU Liming, et al. Analysis on the use of excrement to treat diseases in Ge hong's Zhouhou beiji Fang[J]. Acta Chinese Medicine, 2019, 34(5): 916-919. doi:10.16368/j.issn.1674-8999.2019.05.218.
[46] 张远真, 曾煜闺, 聂晓晶. 粪菌移植在儿科应用的研究进展[J]. 中华实用儿科临床杂志, 2022, 37(4): 311-314. doi:10.3760/cma.j.cn101070-20200824-01401. ZHANG Yuanzhen, ZENG Yugui, NIE Xiaojing. Research progress of the application of fecal microbiota transplantation in pediatric diseases[J]. Chinese Journal of Applied Clinical Pediatrics, 2022, 37(4): 311-314. doi:10.3760/cma.j.cn101070-20200824-01401.
[47] Zhang FM, Cui BT, He XX, et al. Microbiota transplantation: concept, methodology and strategy for its modernization[J]. Protein Cell, 2018, 9(5): 462-473. doi:10.1007/s13238-018-0541-8.
[48] Antushevich H. Fecal microbiota transplantation in disease therapy[J]. Clin Chim Acta, 2020, 503: 90-98. doi:10.1016/j.cca.2019.12.010.
[49] Colman RJ, Rubin DT. Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis[J]. J Crohns Colitis, 2014, 8(12): 1569-1581. doi:10.1016/j.crohns.2014.08.006.
[50] Khoruts A, Sadowsky MJ. Understanding the mechanisms of faecal microbiota transplantation[J]. Nat Rev Gastroenterol Hepatol, 2016, 13(9): 508-516. doi:10.1038/nrgastro.2016.98.
[51] Xu MQ, Cao HL, Wang WQ, et al. Fecal microbiota transplantation broadening its application beyond intestinal disorders[J]. World J Gastroenterol, 2015, 21(1): 102-111. doi:10.3748/wjg.v21.i1.102.
[52] Wang YH, Wiesnoski DH, Helmink BA, et al. Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis[J]. Nat Med, 2018, 24(12): 1804-1808. doi:10.1038/s41591-018-0238-9.
[53] Burrello C, Giuffrè MR, Macandog AD, et al. Fecal microbiota transplantation controls murine chronic intestinal inflammation by modulating immune cell functions and gut microbiota composition[J]. Cells, 2019, 8(6): E517. doi:10.3390/cells8060517.
[54] Feehley T, Plunkett CH, Bao RY, et al. Healthy infants harbor intestinal bacteria that protect against food allergy[J]. Nat Med, 2019, 25(3): 448-453. doi:10.1038/s41591-018-0324-z.
[55] Rachid R, Stephen-Victor E, Chatila TA. The microbial origins of food allergy[J]. J Allergy Clin Immunol, 2021, 147(3): 808-813. doi:10.1016/j.jaci.2020.12.624.
[56] Albuhairi S, Rachid R. Novel therapies for treatment of food allergy[J]. Immunol Allergy Clin North Am, 2020, 40(1): 175-186. doi:10.1016/j.iac.2019.09.007.
[57] 朱忠生, 郑跃杰, 蔡华波, 等. 粪菌移植治疗幼儿严重食物过敏性胃肠病1例并文献复习[J]. 临床儿科杂志, 2017, 35(4): 247-252. doi:10.3969/j.issn.1000-3606.2017.04.002. ZHU Zhongsheng, ZHENG Yuejie, CAI Huabo, et al. Fecal bacteria transplantation for treatment of severe gastrointestinal disease caused by food allergy in children: a case report and literature review[J]. Journal of Clinical Pediatrics, 2017, 35(4): 247-252. doi:10.3969/j.issn.1000-3606.2017.04.002.
[58] Berin MC. Dysbiosis in food allergy and implications for microbial therapeutics [J]. J Clin Invest, 2021, 131(2): e144994. doi:10.1172/JCI144994.
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[8] 冯云1,2 ,李文婷3 ,唐平章1 ,徐震纲1 ,张彬1 ,王乃利3
. 胸背动脉穿支皮瓣的解剖学研究
及其在头颈修复中的意义
[J]. 山东大学耳鼻喉眼学报, 2009, 23(2): 20 -23 .
[9] 梁利伟. 唇龈沟径路治疗鼻中隔软骨前脱位[J]. 山东大学耳鼻喉眼学报, 2009, 23(3): 50 -51 .
[10] 邓享坤,王金泉,邱志宏,邓秀玉. 鼻内镜下鼻腔鼻窦血管瘤切除术[J]. 山东大学耳鼻喉眼学报, 2010, 24(01): 43 .