Gut microbiota bacterial depletions and altered metabolic activity at 3 months are implicated in childhood atopy and asthma1. 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.
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This study was supported by the US National Institutes of Health and National Institute of Allergy and Infectious Diseases P01 AI089473-01 (C.C.J., D.R.O., H.A.B., N.W.L., S.V.L., G.W., and E.M.Z.) and the Alfred P. Sloan Foundation 2013-6-03 (S.V.L.). We thank C. Arrieta and B. Finlay for graciously sharing sequencing data from the CHILD study.
The authors declare no competing financial interests.
Supplementary Figures 1–9 and Supplementary Tables 1–2, 8–10; Supplementary Note (PDF 4354 kb)
Association between early life factors and IGMs (XLS 55 kb)
Association between early life factors and NGMs (XLS 46 kb)
Factors tested for possible confounding effect on the risk of developing PM atopy for NGM (XLS 50 kb)
Bacterial taxa exhibiting significantly increased relative abundance in low-risk NGM1 versus the high-risk NGM3 neonatal gut microbiota (XLSX 77 kb)
Bacterial taxa exhibiting significantly increased relative abundance in low-risk NGM2 versus the high-risk NGM3 neonatal gut microbiota (XLSX 78 kb)
Metabolites significantly enriched in low-risk NGM1 versus high-risk NGM3 neonatal gut microbiota. (XLS 40 kb)
Metabolites significantly enriched in low-risk NGM2 versus high-risk NGM3 neonatal gut microbiota (XLS 46 kb)
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Fujimura, K., Sitarik, A., Havstad, S. et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat Med 22, 1187–1191 (2016). https://doi.org/10.1038/nm.4176
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