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J Allergy Clin Immunol. 2014 Aug 8. pii: S0091-6749(14)00893-8. doi: 10.1016/j.jaci.2014.06.027. [Epub ahead of print]  Perinatal antibiotic-induced shifts in gut microbiota have differential effects on inflammatory lung diseases.  Russell SL1, Gold MJ2, Reynolds LA3, Willing BP4, Dimitriu P5, Thorson L3, Redpath SA5, Perona-Wright G5, Blanchet MR6, Mohn WW5, Brett Finlay B7, McNagny KM8.

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.

PMID: 25145536