Abstract
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 6–8 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.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.
Highlights
Antibiotic exposure alters the microbiota, which can impact the inflammatory immune responses
Microbiota depletion prior to mechanical ventilation aggravated high tidal volume (HTV) ventilation-induced worsening of lung function To investigate the impact of antibiotic-treatment-related disruption of the microbiome on ventilator-induced lung injury we measured parameters of lung function
The static compliance at the beginning of the ventilation showed no difference within the groups (Fig. 1b), whereas the static compliance was reduced in microbiota-depleted HTV-ventilated mice, compared to control mice after 4 h of ventilation (Fig. 1c)
Summary
Antibiotic exposure alters the microbiota, which can impact the inflammatory immune responses. 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). Patients in intensive care units (ICU) are often subjected to MV, which can induce local and systemic inflammatory responses, thereby leading to the development of ventilator-induced lung injury (VILI) [1, 2]. Clarke et al revealed that components of the microbiota, after translocation from the gut into the bloodstream, regulate the inflammatory activity of neutrophilic granulocytes [16] This might be helpful for the host in the case of infection, but might be harmful within the context of autoimmunity or tissue trauma-induced inflammation caused by e.g. MV
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