Ventilator-induced lung injury is aggravated by antibiotic mediated microbiota depletion in mice
Sandra-Maria Wienhold,
Mario Macrì,
Geraldine Nouailles,
Kristina Dietert,
Corinne Gurtner,
Achim D Gruber,
Markus M Heimesaat,
Jasmin Lienau,
Fabian Schumacher,
Burkhard Kleuser,
Bastian Opitz,
Norbert Suttorp,
Martin Witzenrath,
Holger C Müller-Redetzky
Affiliations
Sandra-Maria Wienhold
Division of Pulmonary Inflammation, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
Mario Macrì
Division of Pulmonary Inflammation, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
Geraldine Nouailles
Division of Pulmonary Inflammation, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
Kristina Dietert
Department of Veterinary Pathology, Freie Universität Berlin
Corinne Gurtner
Department of Veterinary Pathology, Freie Universität Berlin
Achim D Gruber
Department of Veterinary Pathology, Freie Universität Berlin
Markus M Heimesaat
Institute for Microbiology and Infection Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
Jasmin Lienau
Division of Pulmonary Inflammation, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
Fabian Schumacher
Department of Nutritional Toxicology, Institute of Nutritional Science, University of Potsdam
Burkhard Kleuser
Department of Nutritional Toxicology, Institute of Nutritional Science, University of Potsdam
Bastian Opitz
Department of Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
Norbert Suttorp
Department of Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
Martin Witzenrath
Division of Pulmonary Inflammation, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
Holger C Müller-Redetzky
Division of Pulmonary Inflammation, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
Abstract Background Antibiotic exposure alters the microbiota, which can impact the inflammatory immune responses. Critically ill patients frequently receive antibiotic treatment and are often subjected to mechanical ventilation, which may induce local and systemic inflammatory responses and development of ventilator-induced lung injury (VILI). The aim of this study was to investigate whether disruption of the microbiota by antibiotic therapy prior to mechanical ventilation affects pulmonary inflammatory responses and thereby the development of VILI. Methods Mice underwent 6–8 weeks of enteral antibiotic combination treatment until absence of cultivable bacteria in fecal samples was confirmed. Control mice were housed equally throughout this period. VILI was induced 3 days after completing the antibiotic treatment protocol, by high tidal volume (HTV) ventilation (34 ml/kg; positive end-expiratory pressure = 2 cmH2O) for 4 h. Differences in lung function, oxygenation index, pulmonary vascular leakage, macroscopic assessment of lung injury, and leukocyte and lymphocyte differentiation were assessed. Control groups of mice ventilated with low tidal volume and non-ventilated mice were analyzed accordingly. Results Antibiotic-induced microbiota depletion prior to HTV ventilation led to aggravation of VILI, as shown by increased pulmonary permeability, increased oxygenation index, decreased pulmonary compliance, enhanced macroscopic lung injury, and increased cytokine/chemokine levels in lung homogenates. Conclusions Depletion of the microbiota by broad-spectrum antibiotics prior to HTV ventilation renders mice more susceptible to developing VILI, which could be clinically relevant for critically ill patients frequently receiving broad-spectrum antibiotics.
