肠道菌群通过短链脂肪酸参与过敏性哮喘气道高反应机制研究进展

doi:10.11852/zgetbjzz2019-0803

摘要/Abstract

摘要： 支气管哮喘(简称哮喘)是一种以可逆性气流阻塞和气道高反应性为特点的气道慢性炎症疾病;短链脂肪酸(SCFAs)是肠道益生菌发酵不易消化的碳水化合物如膳食纤维、抗性淀粉等生成的产物,不仅是机体重要的能量来源,还是重要的免疫信号分子,血液中SCFAs浓度升高对肺部过敏性炎症起保护作用。大量研究表明哮喘发生与肠道菌群变化密切相关。本文从ERK1/2信号通路、TGF-β1/Smads信号传导通路、GPR41 和 GPR43的表达三个方面综述了肠道菌群通过短链脂肪酸参与哮喘气道高反应的可能发生分子机制,为哮喘的治疗提供潜在的新靶点。

关键词: 支气管哮喘, 肠道菌群, 短链脂肪酸, 气道高反应, 信号通路

Abstract: Bronchial asthma (asthma) is a chronic airway inflammatory disease characterized by reversible airflow obstruction and airway hyperresponsiveness.Short-chain fatty acids (SCFAs),as the products of indigestible carbohydrates such as dietary fiber and resistant starch produced by intestinal probiotics,are not only the important energy source for the body,but also important immune signal molecules.The increasing concentration of SCFAs in the blood plays a protective role in pulmonary allergic inflammation.A large number of studies have shown that the occurrence of asthma is closely related to the changes of intestinal flora.This paper summarizes the possible molecular mechanism of intestinal flora participating in asthma airway hyperresponsiveness through short-chain fatty acids from the three aspects of ERK1/2 signaling pathway,TGF-β1/Smads signaling pathway,and GPR41 and GPR43 expression,thereby providing a potential new target for the treatment of asthma.

Key words: bronchial asthma, intestinal flora, short-chain fatty acids, airway hyperresponsiveness, signaling pathway

中图分类号:

R725.6

何学佳, 朱薇薇, 毕玫荣. 肠道菌群通过短链脂肪酸参与过敏性哮喘气道高反应机制研究进展[J]. 中国儿童保健杂志, 2020, 28(4): 431-434.

HE Xue-jia, ZHU Wei-wei, BI Mei-rong. Research progress on the mechanism of gut microbiota participating in airway hyperresponsiveness of allergic asthma through short-chain fatty acids[J]. journal1, 2020, 28(4): 431-434.

参考文献

[1] Murphy VE,Powell H,Wark PA,et al.A prospective study of respiratory viral infection in pregnant women with and without asthm[J].Chest,2013,144 (2):420-427.
[2] Nicolas GR,Chang PV.Deciphering the chemical lexicon of host-gut microbiota interactions[J].Trends Pharmacol Sci,2019,40(6):430-445.
[3] Rautava S.Microbial composition of the initial colonization of newborns[J].Nestle Nutr Inst Workshop Ser,2017,88:11-21.
[4] Hu Y,Jin P,Peng J,et al.Different immunological respon-sestoearly-lifeantibiotic exposure affecting auto immunedia-betes development in NOD mice[J].J Autoimmun,2016,72:47-56.
[5] Goto Y,Kiyono H.Epithelial barrier:an interface for the cro ss-communication between gut flora and immune system[J].Immunol Rev,2012,245(1):147-163.
[6] BjÖrkstén,Naaber,Sepp,et al.The intestinal microflora in allergic Estonian and Swedish 2-year-old children[J].Clin Exp Allergy,2010,29(3):342-346.
[7] Sepp E,Julge K,Vasar M,et al.Intestinal microflora of Estonian and Swedish infants[J].Acta Paediatrica,1997,86(9):956-961.
[8] Peuker K,Muff S,Wang J et al.Epithelialcalcineurin controls Mi-crobiota-dependent intestinal tumor development [J] .Nat Med,2016,22(5):506-515.
[9] Zhao L,Zhang F,Ding X,et al.Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes[J].Science,2018,359(6380):1151-1156.
[10] Gomez MDA,Ganalvonarburg SC,Fuhrer T,et al.The maternal microbiota drives early postnatal innate immune development[J].Science,2016,351(6279):1296.
[11] Markle JG,Frank DN,Mortin-Toth S,et al.Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity[J].Science,2013,339(6123):1084-1088.
[12] Mariño E,Richards JL,Mcleod KH,et al.Erratum:gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes[J].Nat Immunol,2017,18(11):1271.
[13] Forsythe P,Inman MD,Bienenstock J,et al.Oral treatment with live lactobacillus reuteri inhibits the allergic airway responsein mice[J].Am J Respir Crit Care Med,2007,175(6):561-569.
[14] Tan J,McKenzie C,Potamitis M,et al.The role of short-chain fatty acids in health and disease[J].Adv Immunol,2014,121(1):91-119.
[15] Kaiko GE,Ryu SH,Koues OI,et al.The colonic crypt protects stem cells from microbiota-derived metabolites[J].Cell,2016,165(7):1708-1720.
[16] Park J,Kim M,Kang SG,et al.Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway[J].Mucosal Immunol,2015,8(1):80.
[17] Vliagoftis H,Kouranos VD,Betsi GI,et al.Probiotics for the treatment of allergic rhinitis and asthma:systematic review of randomized controlled trials[J].Ann Allergy Asthma Immunol,2008,101(6):570-579.
[18] 白晶,刘先胜,徐永健,等.ERK在慢性哮喘大鼠气道平滑肌细胞增殖中的作用[J].中国病理生理杂志,2008,24(3):417-422.
[19] Gao X,Wu G,Gu X,et al.Kruppel-like factor 15 modulates renal interstitial fibrosis by ERK /MAPK and JNK /MAPKpathways regulation [J].Kidney Blood Press Res,2013,37(6):631-640.
[20] Chen JX,Zhang BN,Sun P,et al.Effects of salmonella on proliferation of mouse gastric carcinoma MFC cells and expression of mouse β-defensin-2[J].Chin J Biologicals,2017,30(3):254-257.
[21] Kim JH,Ellwood PE,Asher MI,et al.Diet and asthma:looking back,moving forward[J].Respir Res,2009,12(10):49.
[22] Sonnenburg JL,BãCkhed F.Diet-microbiota interactions as moderators of human metabolism[J].Nature,2016,535(7610):56-64.
[23] Le CE,Nielsen T, Qin J .Richness of human gut microbiome correlates with meta bolic markers[J].Nature,2013,500(7464):541-546.
[24] Rosendahl A,Checchin D,Fehniger TE,et al.Activation of the TGF-beta/activin-Smad2 pathway during allergic airway inflammation[J].Am J Resp Cell Mol,2001,25(1):60-68.
[25] 徐毛冶,黄茂,蒋理,等.转化生长因子β1与支气管哮喘的相关研究[J].内蒙古医学杂志,2005,37(2):101-102.
[26] Kim MH,Kang SG,Park JH,et al.Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice[J].Gastroenterology,2013,145(2):396-406.
[27] Kim S,Kim YM,Kwak YS.A novel therapeutic target,GPR43;Where it stands in drug discovery[J].Arch Pharm Res,2012,35(9):1505-1509.
[28] Brown AJ,Goldsworthy SM,Barnes AA,et al.The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids.[J].J Biol Chem,2003,278(13):11312-11319.
[29] 马钰,刘兰德,刘方,等.丁酸钠及其G蛋白偶联受体对T淋巴细胞的调节作用[J].现代免疫学,2012,32(6):501-505.
[30] Maslowski KM,Vieira AT,Ng A,et al.Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43[J].Nature,2009,461(7268):1282-1286.
[31] Zmora N,Zilberman-Schapira G,Suez J,et al.Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features[J].Cell,2018,174(6):1388-1405.
[32] Ooijevaar RE,Terveer EM.Clinical application and potential of fecal microbiota transplantation[J].Annu Rev Med,2019,70:335-351.