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J Allergy Clin Immunol. 2015 Jan;135(1):100-9. doi: 10.1016/j.jaci.2014.06.027. Epub 2014 Aug 18.

Perinatal antibiotic-induced shifts in gut microbiota have differential effects on inflammatory lung diseases.

Author information

1
Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
2
Biomedical Research Center, University of British Columbia, Vancouver, British Columbia, Canada.
3
Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
4
Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada; Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
5
Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada; Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
6
Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, Quebec, Canada.
7
Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: bfinlay@interchange.ubc.ca.
8
Biomedical Research Center, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: Kelly@brc.ubc.ca.

Abstract

BACKGROUND:

Resident gut microbiota are now recognized as potent modifiers of host immune responses in various scenarios. Recently, we demonstrated that perinatal exposure to vancomycin, but not streptomycin, profoundly alters gut microbiota and enhances susceptibility to a TH2 model of allergic asthma.

OBJECTIVE:

Here we sought to further clarify the etiology of these changes by determining whether perinatal antibiotic treatment has a similar effect on the TH1/TH17-mediated lung disease, hypersensitivity pneumonitis.

METHODS:

Hypersensitivity pneumonitis was induced in C57BL/6 wild-type or recombination-activating gene 1-deficient mice treated perinatally with vancomycin or streptomycin by repeated intranasal administration of Saccharopolyspora rectivirgula antigen. Disease severity was assessed by measuring lung inflammation, pathology, cytokine responses, and serum antibodies. Microbial community analyses were performed on stool samples via 16S ribosomal RNA pyrosequencing and correlations between disease severity and specific bacterial taxa were identified.

RESULTS:

Surprisingly, in contrast to our findings in an allergic asthma model, we found that the severity of hypersensitivity pneumonitis was unaffected by vancomycin, but increased dramatically after streptomycin treatment. This likely reflects an effect on the adaptive, rather than innate, immune response because the effects of streptomycin were not observed during the early phases of disease and were abrogated in recombination-activating gene 1-deficient mice. Interestingly, Bacteroidetes dominated the intestinal microbiota of streptomycin-treated animals, while vancomycin promoted the expansion of the Firmicutes.

CONCLUSIONS:

Perinatal antibiotics exert highly selective effects on resident gut flora, which, in turn, lead to very specific alterations in susceptibility to TH2- or TH1/TH17-driven lung inflammatory disease.

KEYWORDS:

Antibiotics; Bacteroidetes; Firmicutes; asthma; gut microbiota; hypersensitivity pneumonitis; perinatal

PMID:
25145536
DOI:
10.1016/j.jaci.2014.06.027
[Indexed for MEDLINE]

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