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

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 Randall Ownby, Edward M. Zoratti, Albert M. Levin, Christine C. Johnson, Susan V. Lynch

Research output: Contribution to journalArticle

200 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1187-1191
Number of pages5
JournalNature Medicine
Volume22
Issue number10
DOIs
StatePublished - Oct 1 2016

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T-cells
Cell Differentiation
T-Lymphocytes
Asthma
Dysbiosis
Rhodotorula
Bifidobacterium
Metabolome
Water
Candida
Microbiota
Metabolites
Fungi
Cell culture
Interleukin-4
Bacteria
Parturition
Gastrointestinal Microbiome
Chemical analysis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Fujimura, K. E., Sitarik, A. R., Havstad, S., Lin, D. L., Levan, S., Fadrosh, D., ... Lynch, S. V. (2016). Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nature Medicine, 22(10), 1187-1191. https://doi.org/10.1038/nm.4176

Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. / Fujimura, Kei E.; Sitarik, Alexandra R.; Havstad, 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 Randall; Zoratti, Edward M.; Levin, Albert M.; Johnson, Christine C.; Lynch, Susan V.

In: Nature Medicine, Vol. 22, No. 10, 01.10.2016, p. 1187-1191.

Research output: Contribution to journalArticle

Fujimura, KE, Sitarik, AR, Havstad, S, Lin, DL, Levan, S, Fadrosh, D, Panzer, AR, Lamere, B, Rackaityte, E, Lukacs, NW, Wegienka, G, Boushey, HA, Ownby, DR, Zoratti, EM, Levin, AM, Johnson, CC & Lynch, SV 2016, 'Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation', Nature Medicine, vol. 22, no. 10, pp. 1187-1191. https://doi.org/10.1038/nm.4176
Fujimura KE, Sitarik AR, Havstad S, Lin DL, Levan S, Fadrosh D et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nature Medicine. 2016 Oct 1;22(10):1187-1191. https://doi.org/10.1038/nm.4176
Fujimura, Kei E. ; Sitarik, Alexandra R. ; Havstad, 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 Randall ; Zoratti, Edward M. ; Levin, Albert M. ; Johnson, Christine C. ; Lynch, Susan V. / Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. In: Nature Medicine. 2016 ; Vol. 22, No. 10. pp. 1187-1191.
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