title: Perinatal antibiotic-induced shifts in gut microbiota have differential effects on inflammatory lung diseases.
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.
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Russell
authors.affiliation: Biomedical Research Center, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gold
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Reynolds
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada; Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Willing
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada; Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Pedro
authors.initials: P
authors.lastname: Dimitriu
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Thorson
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada; Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Redpath
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada; Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Georgia
authors.initials: G
authors.lastname: Perona-Wright
authors.affiliation: Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, Quebec, Canada.
authors.forename: Marie-Renée
authors.initials: MR
authors.lastname: Blanchet
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada; Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: William W
authors.initials: WW
authors.lastname: Mohn
authors.affiliation: 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.
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
authors.affiliation: Biomedical Research Center, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: Kelly@brc.ubc.ca.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McNagny
mesh_terms: D000542:Alveolitis, Extrinsic Allergic / Q000097:blood / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D016207:Cytokines / Q000276:immunology; D041981:Gastrointestinal Tract / Q000382:microbiology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008810:Mice, Inbred C57BL; D064307:Microbiota; D016930:Saccharopolyspora; D012720:Severity of Illness Index; D013307:Streptomycin / Q000009:adverse effects*; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D007074:Immunoglobulin G; D014640:Vancomycin; D013307:Streptomycin
keywords: Antibiotics; Bacteroidetes; Firmicutes; asthma; gut microbiota; hypersensitivity pneumonitis; perinatal