TY  - JOUR
A1  - Wienhold, Sandra-Maria
A1  - Macri, Mario
A1  - Nouailles, Geraldine
A1  - Dietert, Kristina
A1  - Gurtner, Corinne
A1  - Gruber, Achim D.
A1  - Heimesaat, Markus M.
A1  - Lienau, Jasmin
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Opitz, Bastian
A1  - Suttorp, Norbert
A1  - Witzenrath, Martin
A1  - Müller-Redetzky, Holger C.
T1  - Ventilator-induced lung injury is aggravated by antibiotic mediated microbiota depletion in mice
JF  - Critical Care
N2  - BackgroundAntibiotic 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.MethodsMice underwent 6-8weeks 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 (34ml/kg; positive end-expiratory pressure=2 cmH(2)O) for 4h. 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.ResultsAntibiotic-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.ConclusionsDepletion 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.
KW  - Broad-spectrum antibiotic therapy
KW  - Ventilator-induced lung injury
KW  - Microbiota
Y1  - 2018
U6  - https://doi.org/10.1186/s13054-018-2213-8
SN  - 1466-609X
SN  - 1364-8535
VL  - 22
IS  - 282
PB  - BMC
CY  - London
ER  -