Modulation of pulmonary microbiota by antibiotic or probiotic aerosol therapy: a new strategy to promote immunosurveillance against lung metastases. Bronchoalveolar lavage (BAL) microbiota of antibiotic-treated and untreated mice

Pulmonary immunological tolerance to inhaled particulates might create a permissive milieu for lung metastasis. Lung microbiota contribute to pulmonary tolerance; here, we explored if its manipulation via antibiotics or probiotics aerosolization favours immune response against melanoma metastasis. In lungs of vancomycin/neomycin aerosolized mice, a decrease in bacterial load was associated to reduced regulatory T cells and enhanced T and NK cells activation, that paralleled a significant reduction of melanoma B16 lung metastases. Reduction of metastases also occurred in lungs transplanted with bacterial isolates from antibiotic-treated lungs. Aerosolized Lactobacillus rhamnosus strongly promoted immunity against B16 lung metastases as well. Furthermore, probiotics or antibiotics improved chemotherapy activity against advanced B16 metastases. Thus, we have identified a previously unappreciated role for lung microbiota in contributing to metastatization and demonstrated for the first time that its targeting via aerosolization is a new therapy to prevent metastases and enhance response to chemotherapy.