615. Can We Restore the Lung Microbiome with Fecal Microbiota Transplant (FMT)?

BACKGROUND: Unabated use of antibiotics for human diseases, in livestock and aquaculture has resulted in natural selection of multi-drug-resistant organisms (MDROs). The emergence of pan-resistant strains of Pseudomonas spp. pose a major threat to patients appropriately exposed to antibiotics (e.g., cystic fibrosis, lung transplant recipients). This organism evades antibiotics by a combination of efflux pumps, harboring multiple-resistant genes and acquiring low permeability of the outer membrane. Altering the gut microbiome could potentially modify the lung microbiome of patients colonized or infected with MDROs. METHODS: A 17-year-old patient with CF developed recurrent exacerbations with an extreme drug-resistant Pseudomonas aeruginosa; due to the lack of effective antibiotics to treat her while awaiting a decision to proceed with lung transplantation, sputum cultures were collected as part of clinical care. We modeled patient-derived isolate of predominantly MDR Pseudomonas in C57Bl6/j mice, where we engrafted the isolate into humanized murine lungs and studied host cytokine responses and microbial composition of the gut and lungs to the engraftment. RESULTS: Our data shows that there is a dominant IL6- and IL17-mediated immune response to the engraftment, accompanied by measurable changes to the lung and gut microbiota. We also show that some of these changes can be reversed by fecal microbial transplant (FMT) of ‘normal’ microbiota into the gut and lungs. CONCLUSION: This murine model results suggest a potential role and effectiveness of gut FMT as a therapeutic measure for MDR bacterial infection in the lungs. Further studies are required to assess response in humans. DISCLOSURES: L. M. Abbo, Roche Diagnostics: Scientific Advisor, Consulting fee.