Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation.

Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation.
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DOI:
10.1038/nm.4176
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发表时间:
2016-10
期刊:
影响因子:
82.9
通讯作者:
Lynch, Susan V.
Lynch, Susan V.
中科院分区:
医学1区
文献类型:
--
作者:
Fujimura, Kei E.;Sitarik, Alexandra R.;Haystad, Suzanne;Lin, Din L.;Levan, Sophia;Fadrosh, Douglas;Panzer, Ariane R.;LaMere, Brandon;Rackaityte, Elze;Lukacs, Nicholas W.;Wegienka, Ganesa;Boushey, Homer A.;Ownby, Dennis R.;Zoratti, Edward M.;Levin, Albert M.;Johnson, Christine C.;Lynch, Susan V.

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改变的婴儿人类肠道微生物组组成和代谢活动与儿童特应性和哮喘有关。我们假设存在组成不同的新生儿肠道微生物群,并且与儿童特应性和哮喘的相对风险(RR)有差异。使用来自美国出生队列的粪便样本(n = 298;年龄1-11个月)和16 S rRNA测序,新生儿(中位年龄35天)可分为三个微生物群组成状态(NGM 1 -3)。两组儿童在两岁时患多敏感性过敏症和在四岁时患医生诊断的哮喘的RR有显著差异。最高风险组NGM 3显示出某些细菌(例如双歧杆菌属、阿克曼氏菌属和粪杆菌属)的相对丰度较低,特定真菌(念珠菌属和红酵母属)的相对丰度较高,以及富含促炎代谢物的独特粪便代谢物组。成人外周血T细胞与来自NGM 3受试者的无菌粪便水的离体培养增加了产生白细胞介素-4的CD 4+细胞的比例,并降低了Foxp 3 + CD 25 + CD 4+细胞的相对丰度。12,13区分NGM 3与低风险NGM的DiHOME概括了NGM 3粪便水对Foxp 3 + CD 25 + CD 4+细胞相对丰度的影响。这些发现表明,新生儿肠道微生物组生态失调驱动与儿童特应性相关的CD 4 + T细胞功能障碍。
Altered infant human gut microbiome composition and metabolic activity are implicated in childhood atopy and asthma. We hypothesized that compositionally distinct neonatal human gut microbiota exist and are differentially related to relative–risk (RR) of childhood atopy and asthma. Using stool samples (n = 298; aged 1–11 months) from a US birth cohort and 16S rRNA sequencing, neonates (median age 35 days) were divisible into three microbiota–composition states (NGM1–3). Each incurred significantly different RR for multi–sensitized atopy at age–two years and doctor–diagnosed asthma at age–four years. The highest risk group, NGM3, showed lower relative abundance of certain bacteria (e.g. Bifidobacterium, Akkermansia and Faecalibacterium), higher relative abundance of particular fungi (Candida and Rhodotorula), and a distinct fecal metabolome enriched for pro-inflammatory metabolites. Ex vivo culture of adult human peripheral T–cells with sterile fecal water from NGM3 subjects increased the proportion of CD4+ cells producing interleukin–4 and reduced the relative abundance of Foxp3+CD25+CD4+ cells. 12,13 DiHOME which discriminated NGM3 from lower–risk NGMs, recapitulated the effect of NGM3 fecal water on Foxp3+CD25+CD4+ cell relative abundance. These findings suggest that neonatal gut microbiome dysbiosis drives CD4+ T–cell dysfunction associated with childhood atopy.
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