儿童肠道分节丝状菌年龄分布特征及其与肠黏膜免疫的关系

刘伟荣, 舒小莉, 顾伟忠, 彭克荣, 赵泓, 陈波, 江丽琴, 江米足

中国当代儿科杂志 ›› 2019, Vol. 21 ›› Issue (6) : 534-540.

PDF(1675 KB)
HTML
PDF(1675 KB)
HTML
中国当代儿科杂志 ›› 2019, Vol. 21 ›› Issue (6) : 534-540. DOI: 10.7499/j.issn.1008-8830.2019.06.007
论著·临床研究

儿童肠道分节丝状菌年龄分布特征及其与肠黏膜免疫的关系

  • 刘伟荣1,2, 舒小莉1, 顾伟忠1, 彭克荣1, 赵泓1, 陈波1, 江丽琴1, 江米足1
作者信息 +

Age distribution characteristics of intestinal segmented filamentous bacteria and their relationship with intestinal mucosal immunity in children

  • LIU Wei-Rong1,2, SHU Xiao-Li1, GU Wei-Zhong1, PENG Ke-Rong1, ZHAO Hong1, CHEN Bo1, JIANG Li-Qin1, JIANG Mi-Zu1
Author information +
文章历史 +

摘要

目的了解儿童肠道分节丝状菌(SFB)年龄分布特征及其与肠道黏膜免疫的关系。方法收集177例儿童的新鲜粪便及47例儿童肠镜检查时的回盲部肠液,采用RT-PCR法测定SFB,ELISA法测定其sIgA浓度。采用免疫组化方法测定23例儿童回肠末端黏膜IL-17A细胞数量和上皮内淋巴细胞数量及Th细胞分化相关的转录因子T-bet、FOXP3和ROR-γt的表达。结果儿童肠道SFB阳性率为19.2%(34/177)。趋势分析显示SFB阳性率随年龄增加呈降低趋势:0岁~、1岁~、2岁~、3岁~、4岁~、5岁~、6岁~、7~15岁分别为40%、47%、32%、15%、12%、13%、15%、4%(P < 0.001)。SFB阳性患儿(24例)的肠液sIgA浓度明显高于SFB阴性患儿(23例)(P < 0.01)。SFB阳性组(12例)回肠末端黏膜上皮细胞内淋巴细胞数量及转录因子T-bet、FOXP3和ROR-γt的表达与SFB阴性组(11例)的差异无统计学意义,而SFB阳性组回肠末端黏膜IL-17A细胞数量明显低于SFB阴性组(P < 0.05)。结论儿童SFB肠道定植与年龄相关,其中3岁以内婴幼儿SFB肠道定植率较高;SFB阳性者肠道sIgA分泌增加,回肠末端IL-17A细胞数量减少。

Abstract

Objective To investigate the age distribution characteristics of intestinal segmented filamentous bacteria (SFB) in children and their relationship with intestinal mucosal immunity. Methods The fresh feces of 177 children and the ileocecal fluid of 47 children during colonoscopy were collected. The SFB was determined by real-time PCR. The concentration of secretory immunoglobulin A (sIgA) was determined by enzyme-linked immunosorbent assay. The numbers of interleukin 17A (IL-17A) cells and intraepithelial lymphocytes in the terminal ileum mucosa and the expression of transcription factors associated with the differentiation of T helper (Th) cells, T-box transcription factor (T-bet), forkhead box P3 (FOXP3), and retinoid-related orphan receptor gamma t (ROR-γt), were determined by immunohistochemistry. Results The positive rate of intestinal SFB in these children was 19.2% (34/177). Trend analysis showed that the positive rate of SFB was correlated with age:the rates for children aged 0-, 1-, 2-, 3-, 4-, 5-, 6-, and 7-15 years were 40%, 47%, 32%, 15%, 12%, 13%, 15% and 4% respectively (P < 0.001). The concentration of sIgA in intestinal fluid was significantly higher in SFB-positive children (n=24) than in SFB-negative children (n=23) (P < 0.01). The number of intraepithelial lymphocytes in the terminal ileum mucosa and the expression of T-bet, FOXP3, and ROR-γt were not significantly different between the SFB-positive group (n=12) and the SFB-negative group (n=11), but the number of IL-17A cells in the terminal ileum mucosa was significantly lower in the SFB-positive group than in the SFB-negative group (P < 0.05). Conclusions Intestinal SFB colonization in children is age-related, and the colonization rate is relatively high in children under 3 years old. In SFB-positive children, the secretion of intestinal sIgA is increased, while the number of IL-17A cells in the terminal ileum is reduced.

关键词

分节丝状菌 / 黏膜免疫 / sIgA / Th17细胞 / 儿童

Key words

Segmented filamentous bacterium / Mucosal immunity / sIgA / Th17 cell / Child

引用本文

导出引用
刘伟荣, 舒小莉, 顾伟忠, 彭克荣, 赵泓, 陈波, 江丽琴, 江米足. 儿童肠道分节丝状菌年龄分布特征及其与肠黏膜免疫的关系[J]. 中国当代儿科杂志. 2019, 21(6): 534-540 https://doi.org/10.7499/j.issn.1008-8830.2019.06.007
LIU Wei-Rong, SHU Xiao-Li, GU Wei-Zhong, PENG Ke-Rong, ZHAO Hong, CHEN Bo, JIANG Li-Qin, JIANG Mi-Zu. Age distribution characteristics of intestinal segmented filamentous bacteria and their relationship with intestinal mucosal immunity in children[J]. Chinese Journal of Contemporary Pediatrics. 2019, 21(6): 534-540 https://doi.org/10.7499/j.issn.1008-8830.2019.06.007

参考文献

[1] Human Microbiome Project Consortium. A framework for Human Microbiome Research[J]. Nature, 2012, 486(7402):215-221.
[2] Chung H, Pamp SJ, Hill JA, et al. Gut immune maturation depends on colonization with a host-specific microbiota[J]. Cell, 2012, 149(7):1578-1593.
[3] Flannigan KL, Denning TL. Segmented filamentous bacteria-induced immune responses:a balancing act between host protection and autoimmunity[J]. Immunology, 2018, 154:537-546.
[4] Liao N, Yin Y, Sun G, et al. Colonization and distribution of segmented filamentous bacteria (SFB) in chicken gastrointestinal tract and their relationship with host immunity[J]. FEMS Microbiol Ecol, 2012, 81(2):395-406.
[5] Ohashi Y, Hiraguchi M, Ushida K. The composition of intestinal bacteria affects the level of luminal IgA[J]. Biosci Biotechnol Biochem, 2006, 70(12):3031-3035.
[6] Yin Y, Wang Y, Zhu L, et al. Comparative analysis of the distribution of segmented filamentous bacteria in humans, mice, and chickens[J]. ISME J, 2013, 7(3):615-621.
[7] Caselli M, Tosini D, Gafa R, et al. Segmented filamentous bacteria-like organisms in histological slides of ileo-cecal valves in patients with ulcerative colitis[J]. Am J Gastroenterol, 2013, 108(5):860-861.
[8] Ge Z, Feng Y, Woods SE, et al. Spatial and temporal colonization dynamics of segmented filamentous bacteria is influenced by gender, age and experimental infection with Helicobacter hepaticus in Swiss Webstar mice[J]. Microbes Infect, 2015, 17(1):16-22.
[9] Finotti A, Gasparello J, Lampronti I, et al. PCR detection of segmented filamentous bacteria in the terminal ileum of patients with ulcerative colitis[J]. BMJ Open Gastroenterol, 2017, 4(1):e000172.
[10] Ericsson AC, Hagan CE, Davis DJ, et al. Segmented filamentous bacteria:commensal microbes with potential effects on research[J]. Comp Med, 2014, 64(2):90-98.
[11] Schnupf P, Gaboriau-Routhiau V, Gros M, et al. Growth and host interaction of mouse segmented filamentous bacteria in vitro[J]. Nature, 2015, 520(7545):99-103.
[12] Turnbaugh PJ, Ridaura VK, Faith JJ, et al. The effect of diet on the human gut microbiome:a metagenomic analysis in humanized gnotobiotic mice[J]. Sci Transl Med, 2009, 1(6):6ra14.
[13] Jin S, Zhao D, Cai C, et al. Low-dose penicillin exposure in early life decreases Th17 and the susceptibility to DSS colitis in mice through gut microbiota modification[J]. Sci Rep, 2017, 7:43662.
[14] Prakash T, Oshima K, Morita H, et al. Complete genome sequences of rat and mouse segmented filamentous bacteria, a potent inducer of Th17 cell differentiation[J]. Cell Host Microbe, 2011, 10(3):273-284.
[15] Sczesnak A, Segata N, Qin X, et al. The genome of Th17 cell-inducing segmented filamentous bacteria reveals extensive auxotrophy and adaptations to the intestinal environment[J]. Cell Host Microbe, 2011, 10(3):260-272.
[16] Suzuki K, Meek B, Doi Y, et al. Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut[J]. Proc Natl Acad Sci U S A, 2004, 101(7):1981-1986.
[17] Brandzaeg P. Mucosal immunity:induction, dissemination, and effector functions[J]. Scand J Immunol, 2009, 70(6):505-515.
[18] Palm NW, de Zoete MR, Cullen TW, et al. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease[J]. Cell, 2014, 158(5):1000-1010.
[19] Klaasen HL, Van der Heijden PJ, Stok W, et al. A pathogenic, intestinal, segmented, filamentous bacteria stimulate the mucosal immune system of mice[J]. Infect Immun, 1993, 61(1):303-306.
[20] Talham GL, Jiang HQ, Bos NA, et al. Segmented filamentous bacteria are potent stimuli of a physiologically normal state of the murine gut mucosal immune system[J]. Infect Immun, 1999, 67(4):1992-2000.
[21] Lamm ME. Interaction of antigens and antibodies at mucosal surfaces[J]. Annu Rev Microbiol, 1997, 51:311-340.
[22] Farkas AM, Panea C, Goto Y, et al. Induction of Th17 cells by segmented filamentous bacteria in the murine intestine[J]. J Immunol Methods, 2015, 421:104-111.
[23] Atarashi K, Tanoue T, Ando M, et al. Th17 cell induction by adhesion of microbes to intestinal epithelial cells[J]. Cell, 2015, 163(2):367-380.
[24] Furusawa Y, ObataY, Hase K. Commensal microbiota regulates T cell fate decision in the gut[J]. Semin Immunopathol, 2015, 37(1):17-25.
[25] Teng F, Klinger CN, Felix KM, et al. Gut microbiota drive autoimmune arthritis by promoting differentiation and migration of Peyer's patch T follicular helper cells[J]. Immunity, 2016, 44(4):875-888.
[26] Ivanov Ⅱ. Microbe hunting hits home[J]. Cell Host Microbe, 2017, 21(3):282-285.

基金

国家重点基础研究发展计划(973)(2013CB531404);国家卫生计生委科学研究基金-浙江省医药卫生重大科技计划(WKJ-ZJ-1622)。


PDF(1675 KB)
HTML

Accesses

Citation

Detail

段落导航
相关文章

/