肺部微生物组与儿童支气管哮喘内型关系的研究进展

李靖燕; 田兆方

doi:10.7499/j.issn.1008-8830.2304056

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中国当代儿科杂志 ›› 2023, Vol. 25 ›› Issue (10) : 1078-1083. DOI: 10.7499/j.issn.1008-8830.2304056

综述

肺部微生物组与儿童支气管哮喘内型关系的研究进展

李靖燕, 田兆方

作者信息 +

Recent research on the relationship between pulmonary microbiome and asthma endotypes in children

LI Jing-Yan, TIAN Zhao-Fang

Author information +

文章历史 +

摘要

目前认为支气管哮喘（简称“哮喘”）不是一种单一的疾病，而是一组具有多种表型且机制涉及多条信号通路的综合征。儿童哮喘通常起源于学龄前期，其病因复杂多样。近年来，随着高通量测序技术的发展，发现早期肺部菌群的改变与哮喘的发生发展有关，并且肺部菌群在不同气道炎症（哮喘内型）之间存在显著差异。因此，了解哮喘儿童肺部菌群特点，有助于控制儿童哮喘的进展及改善预后，为哮喘患儿的诊治提供新的思路。

Abstract

Bronchial asthma is not considered a singular disease, but rather a collection of syndromes with multiple phenotypes and mechanisms that involve various signaling pathways. It typically emerges during the preschool years, and its etiology is intricate and diverse. In recent years, the advancement of high-throughput sequencing technology has revealed that early alterations in lung microbiota may be associated with asthma incidence and progression. Moreover, significant variations in lung microbiota have been observed among different airway inflammation profiles, known as asthma endotypes. Hence, a comprehensive understanding of the characteristics of lung microbiota in children with asthma can aid in managing disease progression and improving long-term prognosis. Additionally, such insights may spark novel approaches to diagnosing and treating childhood asthma.

导出引用

李靖燕, 田兆方. 肺部微生物组与儿童支气管哮喘内型关系的研究进展[J]. 中国当代儿科杂志. 2023, 25(10): 1078-1083 https://doi.org/10.7499/j.issn.1008-8830.2304056

LI Jing-Yan, TIAN Zhao-Fang. Recent research on the relationship between pulmonary microbiome and asthma endotypes in children[J]. Chinese Journal of Contemporary Pediatrics. 2023, 25(10): 1078-1083 https://doi.org/10.7499/j.issn.1008-8830.2304056

参考文献

1 李丽香, 林淑珍, 张任攀, 等. 中国农村儿童哮喘患病情况的Meta分析[J]. 中国当代儿科杂志, 2020, 22(4): 380-386. PMID: 32312379. PMCID: PMC7389704. DOI: 10.7499/j.issn.1008-8830.1910164.
2 Stikker BS, Hendriks RW, Stadhouders R. Decoding the genetic and epigenetic basis of asthma[J]. Allergy, 2023, 78(4): 940-956. PMID: 36727912. DOI: 10.1111/all.15666.
3 Paciência I, Cavaleiro Rufo J, Moreira A. Environmental inequality: air pollution and asthma in children[J]. Pediatr Allergy Immunol, 2022, 33(6): e13818. PMID: 35754123. DOI: 10.1111/pai.13818.
4 van Meel ER, Mensink-Bout SM, den Dekker HT, et al. Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children[J]. Eur Respir J, 2022, 60(4): 2102395. PMID: 35487537. PMCID: PMC9535116. DOI: 10.1183/13993003.02395-2021.
5 Alwarith J, Kahleova H, Crosby L, et al. The role of nutrition in asthma prevention and treatment[J]. Nutr Rev, 2020, 78(11): 928-938. PMID: 32167552. PMCID: PMC7550896. DOI: 10.1093/nutrit/nuaa005.
6 Arrieta MC, Stiemsma LT, Dimitriu PA, et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma[J]. Sci Transl Med, 2015, 7(307): 307ra152. PMID: 26424567. DOI: 10.1126/scitranslmed.aab2271.
7 Whiteside SA, McGinniss JE, Collman RG. The lung microbiome: progress and promise[J]. J Clin Invest, 2021, 131(15): e150473. PMID: 34338230. PMCID: PMC8321564. DOI: 10.1172/JCI150473.
8 康小会, 曹玲. 对儿童哮喘个体精准治疗若干问题的思考[J]. 中国实用儿科杂志, 2020, 35(3): 191-195. DOI: 10.19538/j.ek2020030606.
9 Chiu CJ, Huang MT. Asthma in the precision medicine era: biologics and probiotics[J]. Int J Mol Sci, 2021, 22(9): 4528. PMID: 33926084. PMCID: PMC8123613. DOI: 10.3390/ijms22094528.
10 Taylor SL, Leong LEX, Choo JM, et al. Inflammatory phenotypes in patients with severe asthma are associated with distinct airway microbiology[J]. J Allergy Clin Immunol, 2018, 141(1): 94-103.e15. PMID: 28479329. DOI: 10.1016/j.jaci.2017.03.044.
11 Huynh M, Crane MJ, Jamieson AM. The lung, the niche, and the microbe: exploring the lung microbiome in cancer and immunity[J]. Front Immunol, 2022, 13: 1094110. PMID: 36733391. PMCID: PMC9888758. DOI: 10.3389/fimmu.2022.1094110.
12 Natalini JG, Singh S, Segal LN. The dynamic lung microbiome in health and disease[J]. Nat Rev Microbiol, 2023, 21(4): 222-235. PMID: 36385637. PMCID: PMC9668228. DOI: 10.1038/s41579-022-00821-x.
13 Valverde-Molina J, García-Marcos L. Microbiome and asthma: microbial dysbiosis and the origins, phenotypes, persistence, and severity of asthma[J]. Nutrients, 2023, 15(3): 486. PMID: 36771193. PMCID: PMC9921812. DOI: 10.3390/nu15030486.
14 Man WH, de SteenhuijsenPiters WA, Bogaert D. The microbiota of the respiratory tract: gatekeeper to respiratory health[J]. Nat Rev Microbiol, 2017, 15(5): 259-270. PMID: 28316330. PMCID: PMC7097736. DOI: 10.1038/nrmicro.2017.14.
15 Hou K, Wu ZX, Chen XY, et al. Microbiota in health and diseases[J]. Signal Transduct Target Ther, 2022, 7(1): 135. PMID: 35461318. PMCID: PMC9034083. DOI: 10.1038/s41392-022-00974-4.
16 Pattaroni C, Watzenboeck ML, Schneidegger S, et al. Early-life formation of the microbial and immunological environment of the human airways[J]. Cell Host Microbe, 2018, 24(6): 857-865.e4. PMID: 30503510. DOI: 10.1016/j.chom.2018.10.019.
17 Wypych TP, Wickramasinghe LC, Marsland BJ. The influence of the microbiome on respiratory health[J]. Nat Immunol, 2019, 20(10): 1279-1290. PMID: 31501577. DOI: 10.1038/s41590-019-0451-9.
18 Dick S, Turner S. The airway microbiome and childhood asthma-what is the link?[J]. Acta Med Acad, 2020, 49(2):156-163. PMID: 33189121. DOI: 10.5644/ama2006-124.294.
19 Wenzel SE. Asthma: defining of the persistent adult phenotypes[J]. Lancet, 2006, 368(9537): 804-813. PMID: 16935691. DOI: 10.1016/S0140-6736(06)69290-8.
20 Conrad LA, Cabana MD, Rastogi D. Defining pediatric asthma: phenotypes to endotypes and beyond[J]. Pediatr Res, 2021, 90(1): 45-51. PMID: 33173175. PMCID: PMC8107196. DOI: 10.1038/s41390-020-01231-6.
21 Busse WW, Kraft M, Rabe KF, et al. Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation[J]. Eur Respir J, 2021, 58(2): 2003393. PMID: 33542055. PMCID: PMC8339540. DOI: 10.1183/13993003.03393-2020.
22 LeMessurier KS, Samarasinghe AE. Eosinophils: nemeses of pulmonary pathogens?[J]. Curr Allergy Asthma Rep, 2019, 19(8): 36. PMID: 31218528. PMCID: PMC6993982. DOI: 10.1007/s11882-019-0867-1.
23 Bisgaard H, Hermansen MN, Buchvald F, et al. Childhood asthma after bacterial colonization of the airway in neonates[J]. N Engl J Med, 2007, 357(15): 1487-1495. PMID: 17928596. DOI: 10.1056/NEJMoa052632.
24 Chun Y, Do A, Grishina G, et al. Integrative study of the upper and lower airway microbiome and transcriptome in asthma[J]. JCI insight, 2020, 5(5): e133707. PMID: 32161195. PMCID: PMC7141394. DOI: 10.1172/jci.insight.133707.
25 Bourgoin-Heck M, Duféal M, Saf S, et al. Staphylococcal sensitization: a correlate of type 2-high inflammation in children with severe asthma[J]. J Allergy Clin Immunol Pract, 2023, 11(2):564-571.e1. PMID: 37113036. DOI: 10.1016/j.jaip.2022.10.026.
26 McCauley K, Durack J, Valladares R, et al. Distinct nasal airway bacterial microbiotas differentially relate to exacerbation in pediatric patients with asthma[J]. J Allergy Clin Immunol, 2019, 144(5): 1187-1197. PMID: 31201890. PMCID: PMC6842413. DOI: 10.1016/j.jaci.2019.05.035.
27 韩蕾, 张旻. 非2型哮喘的发病机制及治疗研究进展[J]. 国际呼吸杂志, 2021, 41(1): 47-52. DOI: 10.3760/cma.j.cn131368-20200401-00239.
28 Ray A, Kolls JK. Neutrophilic inflammation in asthma and association with disease severity[J]. Trends Immunol, 2017, 38(12): 942-954. PMID: 28784414. PMCID: PMC5711587. DOI: 10.1016/j.it.2017.07.003.
29 Hossain FMA, Choi JY, Uyangaa E, et al. The interplay between host immunity and respiratory viral infection in asthma exacerbation[J]. Immune Netw, 2019, 19(5): e31. PMID: 31720042. PMCID: PMC6829071. DOI: 10.4110/in.2019.19.e31.
30 Green BJ, Wiriyachaiporn S, Grainge C, et al. Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma[J]. PLoS One, 2014, 9(6): e100645. PMID: 24955983. PMCID: PMC4067344. DOI: 10.1371/journal.pone.0100645.
31 Marathe SJ, Snider MA, Flores-Torres AS, et al. Human matters in asthma: considering the microbiome in pulmonary health[J]. Front Pharmacol, 2022, 13: 1020133. PMID: 36532717. PMCID: PMC9755222. DOI: 10.3389/fphar.2022.1020133.
32 Patel KK, Vicencio AG, Du Z, et al. Infectious Chlamydia pneumoniae is associated with elevated interleukin-8 and airway neutrophilia in children with refractory asthma[J]. Pediatr Infect Dis J, 2010, 29(12): 1093-1098. PMID: 21155094. DOI: 10.1097/inf.0b013e3181eaebdc.
33 Papaioannou AI, Fouka E, Ntontsi P, et al. Paucigranulocyticasthma: potential pathogenetic mechanisms, clinical features and therapeutic management[J]. J Pers Med, 2022, 12(5):850. PMID: 35629272. PMCID: PMC9145917. DOI: 10.3390/jpm12050850.
34 Tliba O, Panettieri RAJr . Paucigranulocytic asthma: uncoupling of airway obstruction from inflammation[J]. J Allergy Clin Immunol, 2019, 143(4): 1287-1294. PMID: 29928921. PMCID: PMC6301131. DOI: 10.1016/j.jaci.2018.06.008.
35 Son JH, Kim JH, Chang HS, et al. Relationship of microbial profile with airway immune response in eosinophilic or neutrophilic inflammation of asthmatics[J]. Allergy Asthma Immunol Res, 2020, 12(3): 412-429. PMID: 32141256. PMCID: PMC7061157. DOI: 10.4168/aair.2020.12.3.412.
36 Durack J, Lynch SV, Nariya S, et al. Features of the bronchial bacterial microbiome associated with atopy, asthma, and responsiveness to inhaled corticosteroid treatment[J]. J Allergy Clin Immunol, 2017, 140(1): 63-75. PMID: 27838347. PMCID: PMC5502827. DOI: 10.1016/j.jaci.2016.08.055.
37 Singanayagam A, Glanville N, Cuthbertson L, et al. Inhaled corticosteroid suppression of cathelicidin drives dysbiosis and bacterial infection in chronic obstructive pulmonary disease[J]. Sci Transl Med, 2019, 11(507): eaav3879. PMID: 31462509. PMCID: PMC7237237. DOI: 10.1126/scitranslmed.aav3879.
38 Dang AT, Marsland BJ. Microbes, metabolites, and the gut-lung axis[J]. Mucosal Immunol, 2019, 12(4):843-850. PMID: 30976087. DOI: 10.1038/s41385-019-0160-6.
39 Wei X, Jiang P, Liu J, et al. Association between probiotic supplementation and asthma incidence in infants: a meta-analysis of randomized controlled trials[J]. J Asthma, 2020, 57(2): 167-178. PMID: 30656984. DOI: 10.1080/02770903.2018.1561893.
40 Chen N, Liu F, Gao Q, et al. A meta-analysis of probiotics for the treatment of allergic airway diseases in children and adolescents[J]. Am J Rhinol Allergy, 2022, 36(4):480-490. PMID: 35238209. DOI: 10.1177/19458924221080159.
41 Voo PY, Wu CT, Sun HL, et al. Effect of combination treatment with Lactobacillus rhamnosus and corticosteroid in reducing airway inflammation in a mouse asthma model[J]. J Microbiol Immunol Infect, 2022, 55(4): 766-776. PMID: 35487817. DOI: 10.1016/j.jmii.2022.03.006.
42 Nembrini C, Sichelstiel A, Kisielow J, et al. Bacterial-induced protection against allergic inflammation through a multicomponent immunoregulatory mechanism[J]. Thorax, 2011, 66(9): 755-763. PMID: 21422039. DOI: 10.1136/thx.2010.152512.
43 Ciprandi G, Tosca MA. Probiotics in children with asthma[J]. Children (Basel), 2022, 9(7): 978. PMID: 35883962. PMCID: PMC9316460. DOI: 10.3390/children9070978.
44 Reddel HK, BacharierLB, Bateman ED, et al. Global initiative for asthma strategy 2021: executive summary and rationale for key changes[J]. Eur Respir J, 2022, 59(1): 2102730. PMID: 34667060. PMCID: PMC8719459. DOI: 10.1183/13993003.02730-2021.
45 Fong I, Zhu J, Finkelstein Y, et al. Antibiotic use in children and youths with asthma: a population-based case-control study[J]. ERJ Open Res, 2021, 7(1): 00944-2020. PMID: 33748257. PMCID: PMC7957291. DOI: 10.1183/23120541.00944-2020.
46 Kelderer F, Mogren I, Eriksson C, et al. Associations between pre- and postnatal antibiotic exposures and early allergic outcomes: a population-based birth cohort study[J]. Pediatr Allergy Immunol, 2022, 33(9): e13848. PMID: 36156813. PMCID: PMC9544930. DOI: 10.1111/pai.13848.
47 LeMessurier KS, Iverson AR, Chang TC, et al. Allergic inflammation alters the lung microbiome and hinders synergistic co-infection with H1N1 influenza virus and Streptococcus pneumoniae in C57BL/6 mice[J]. Sci Rep, 2019, 9(1): 19360. PMID: 31852944. PMCID: PMC6920369. DOI: 10.1038/s41598-019-55712-8.
48 Pollock J, Chalmers JD. The immunomodulatory effects of macrolide antibiotics in respiratory disease[J]. Pulm Pharmacol Ther, 2021, 71: 102095. PMID: 34740749. PMCID: PMC8563091. DOI: 10.1016/j.pupt.2021.102095.
49 Sun J, Li Y. Long-term, low-dose macrolide antibiotic treatment in pediatric chronic airway diseases[J]. Pediatr Res, 2022, 91(5): 1036-1042. PMID: 34120139. PMCID: PMC9122820. DOI: 10.1038/s41390-021-01613-4.
50 Hinks TSC, Levine SJ, Brusselle GG. Treatment options in type-2 low asthma[J]. Eur Respir J, 2021, 57(1): 2000528. PMID: 32586877. PMCID: PMC7116624. DOI: 10.1183/13993003.00528-2020.