肠道菌群与婴幼儿过敏及哮喘密切相关

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

DOI：
10.1038/nm.4176

Abstract：
Gut microbiota bacterial depletions and altered metabolic activity at 3 months are implicated in childhood atopy and asthma. We hypothesized that compositionally distinct human neonatal gut microbiota (NGM) 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 d) were divisible into three microbiota composition states (NGM1~3). Each incurred a substantially different RR for multisensitized atopy at age 2 years and doctor diagnosed asthma at age 4 years. The highest risk group, labeled NGM3, showed lower relative abundance of certain bacteria (for example, 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 human adult peripheral T cells with sterile fecal water from NGM3 subjects increased the proportion of CD4(+) cells producing interleukin (IL)-4 and reduced the relative abundance of CD4(+)CD25(+)FOXP3(+) cells. 12,13-DiHOME, enriched in NGM3 versus lower-risk NGM states, recapitulated the effect of NGM3 fecal water on relative CD4(+)CD25(+)FOXP3(+) cell abundance. These findings suggest that neonatal gut microbiome dysbiosis might promote CD4(+) T cell dysfunction associated with childhood atopy.

All Authors：
Kei E Fujimura,Alexandra R Sitarik,Suzanne Havstad,Din L Lin,Sophia Levan,Douglas Fadrosh,Ariane R Panzer,Brandon LaMere,Elze Rackaityte,Nicholas W Lukacs,Ganesa Wegienka,Homer A Boushey,Dennis R Ownby,Edward M Zoratti,Albert M Levin,Christine C Johnson,Susan V Lynch

First Authors：
Kei E Fujimura

Correspondence：
Susan V Lynch

内容要点：

1、 婴儿3个月时肠道细菌的减少及代谢活性的改变与特应性及哮喘相关；

2、 对美国的298名婴儿（1-11个月大）的粪便样品进行分析，发现新生儿肠道菌群的组成可分为3种状态；

3、 每一种状态导致不同的多重敏感特应性（2岁时）及哮喘（4岁时）的相对风险；

4、 相对风险最高的一组中，双歧杆菌属、Akk菌及Faecalibacterium丰度较低，Candida及Rhodotorula两种真菌的相对丰度较高；

5、 且分泌IL-4的CD4+ T细胞比例增加，而Treg比例降低。