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Nat Med. 2016 Oct;22(10):1187-1191. doi: 10.1038/nm.4176. Epub 2016 Sep 12.

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

Author information

1
Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
2
Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA.
3
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
4
Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
5
Section of Allergy-Immunology, Augusta University, Augusta, Georgia, USA. .
6
Department of Internal Medicine, Division of Allergy and Immunology, Henry Ford Health System, Detroit, Michigan, USA.

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.

Comment in

PMID:
27618652
PMCID:
PMC5053876
DOI:
10.1038/nm.4176
[Indexed for MEDLINE]
Free PMC Article

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