PMID- 29967529
OWN - NLM
STAT- MEDLINE
DCOM- 20191022
LR  - 20191022
IS  - 1530-0447 (Electronic)
IS  - 0031-3998 (Print)
IS  - 0031-3998 (Linking)
VI  - 84
IP  - 3
DP  - 2018 Sep
TI  - Early-life antibiotics attenuate regulatory T cell generation and increase the 
      severity of murine house dust mite-induced asthma.
PG  - 426-434
LID - 10.1038/s41390-018-0031-y [doi]
AB  - INTRODUCTION: Early-life exposure to antibiotics (ABX) has been linked to 
      increases in asthma severity and prevalence in both children and laboratory 
      animals. We explored the immunologic mechanisms behind this association using a 
      mouse model of house dust mite (HDM)-induced asthma and early-life ABX exposure. 
      METHODS: Mice were exposed to three short courses of ABX following weaning and 
      experimental asthma was thereafter induced. Airway cell counts and differentials; 
      serum immunoglobulin E (IgE); pulmonary function; lung histopathology; pulmonary 
      regulatory T cells (Tregs); and the fecal microbiome were characterized following 
      ABX exposure and induction of experimental asthma. RESULTS: Asthma severity was 
      increased in mice exposed to ABX, including: airway eosinophilia, airway 
      hyper-reactivity, serum HDM-specific IgE, and lung histopathology. ABX treatment 
      led to sharp reduction in fecal microbiome diversity, including the loss of 
      pro-regulatory organisms such as Lachnospira. Pulmonary Tregs were reduced with 
      ABX treatment, and this reduction was directly proportional to diminished 
      microbiome diversity. CONCLUSION: Intermittent exposure to ABX early in life 
      worsened the severity of experimental asthma and reduced pulmonary Tregs; the 
      latter change correlated with decreased microbiome diversity. These data may 
      suggest targets for immunologic or probiotic therapy to counteract the harmful 
      effects of childhood ABX.
FAU - Adami, Alexander J
AU  - Adami AJ
AD  - Department of Immunology, University of Connecticut Health, Farmington, CT, USA.
FAU - Bracken, Sonali J
AU  - Bracken SJ
AD  - Department of Immunology, University of Connecticut Health, Farmington, CT, USA.
FAU - Guernsey, Linda A
AU  - Guernsey LA
AD  - Department of Immunology, University of Connecticut Health, Farmington, CT, USA.
AD  - Department of Pediatrics, University of Connecticut Health, Farmington, CT, USA.
FAU - Rafti, Ektor
AU  - Rafti E
AD  - Department of Pediatrics, University of Connecticut Health, Farmington, CT, USA.
FAU - Maas, Kendra R
AU  - Maas KR
AD  - Microbial Analysis, Resources, and Services Facility, University of Connecticut, 
      Storrs, CT, USA.
FAU - Graf, Joerg
AU  - Graf J
AD  - Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, 
      USA.
FAU - Matson, Adam P
AU  - Matson AP
AD  - Department of Immunology, University of Connecticut Health, Farmington, CT, USA.
AD  - Department of Pediatrics, University of Connecticut Health, Farmington, CT, USA.
AD  - Division of Neonatology, Connecticut Children's Medical Center, Hartford, CT, 
      USA.
FAU - Thrall, Roger S
AU  - Thrall RS
AD  - Department of Immunology, University of Connecticut Health, Farmington, CT, USA.
FAU - Schramm, Craig M
AU  - Schramm CM
AD  - Department of Pediatrics, University of Connecticut Health, Farmington, CT, USA. 
      cschramm@uchc.edu.
AD  - Division of Pulmonary Medicine, Connecticut Children's Medical Center, Hartford, 
      CT, USA. cschramm@uchc.edu.
LA  - eng
GR  - F30 HL122018/HL/NHLBI NIH HHS/United States
GR  - F30 HL126324/HL/NHLBI NIH HHS/United States
GR  - R01 AI043573/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180702
PL  - United States
TA  - Pediatr Res
JT  - Pediatric research
JID - 0100714
RN  - 0 (Allergens)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Cytokines)
RN  - 0 (RNA, Ribosomal, 16S)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Airway Remodeling
MH  - Allergens/immunology
MH  - Animals
MH  - Anti-Bacterial Agents/*adverse effects/pharmacology
MH  - Asthma/*epidemiology/*etiology
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Feces/microbiology
MH  - Female
MH  - Immunoglobulin E/blood
MH  - Lung/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microbiota
MH  - Prevalence
MH  - *Pyroglyphidae
MH  - RNA, Ribosomal, 16S/genetics
MH  - Respiratory Function Tests
MH  - T-Lymphocytes, Regulatory/*cytology
MH  - Th2 Cells/cytology
PMC - PMC6258300
MID - NIHMS959853
COIS- Author Disclosures: The authors declare no conflicts of interest related to this 
      study.
EDAT- 2018/07/04 06:00
MHDA- 2019/10/23 06:00
PMCR- 2019/01/02
CRDT- 2018/07/04 06:00
PHST- 2017/09/25 00:00 [received]
PHST- 2018/04/10 00:00 [accepted]
PHST- 2018/03/29 00:00 [revised]
PHST- 2018/07/04 06:00 [pubmed]
PHST- 2019/10/23 06:00 [medline]
PHST- 2018/07/04 06:00 [entrez]
PHST- 2019/01/02 00:00 [pmc-release]
AID - 10.1038/s41390-018-0031-y [pii]
AID - 10.1038/s41390-018-0031-y [doi]
PST - ppublish
SO  - Pediatr Res. 2018 Sep;84(3):426-434. doi: 10.1038/s41390-018-0031-y. Epub 2018 
      Jul 2.