Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation.
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.
Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Kei E
KE
Fujimura
Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA.
Alexandra R
AR
Sitarik
Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA.
Suzanne
S
Havstad
Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Din L
DL
Lin
Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Sophia
S
Levan
Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Douglas
D
Fadrosh
Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Ariane R
AR
Panzer
Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Brandon
B
LaMere
Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Elze
E
Rackaityte
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Nicholas W
NW
Lukacs
Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA.
Ganesa
G
Wegienka
Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Homer A
HA
Boushey
Section of Allergy-Immunology, Augusta University, Augusta, Georgia, USA. .
Dennis R
0000-0003-0944-6466
DR
Ownby
Department of Internal Medicine, Division of Allergy and Immunology, Henry Ford Health System, Detroit, Michigan, USA.
Edward M
EM
Zoratti
Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA.
Albert M
AM
Levin
Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA.
Christine C
CC
Johnson
Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Susan V
SV
Lynch
D001249:Asthma / Q000453:epidemiology* / Q000276:immunology; D001644:Bifidobacterium / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002175:Candida / Q000235:genetics; D002454:Cell Differentiation / Q000276:immunology; D002675:Child, Preschool; D000070036:Faecalibacterium / Q000235:genetics; D005243:Feces / Q000737:chemistry; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D000069196:Gastrointestinal Microbiome / Q000235:genetics* / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology* / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology; D008297:Male; D016017:Odds Ratio; D012336:RNA, Ribosomal, 16S / Q000235:genetics*; D012248:Rhodotorula / Q000235:genetics; D017423:Sequence Analysis, RNA; D013601:T-Lymphocytes / Q000276:immunology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D012336:RNA, Ribosomal, 16S; D015847:Interleukin-4