Disruption of the gut microbiome augments the development of ventilator-induced lung injury in mice

Background:

The gut microbiome calibrates the local and extra intestinal immune system during development and regulation in conditions like autoimmunity, allergy and infection. Recent studies revealed a significant impact of the gut microbiome on the pulmonary inflammatory response and related lung injury. The gut microbiome is disturbed in critically ill patients as broad-spectrum antibiotics and selective decontamination of the digestive tract (SDD) are frequently applied. Critically ill patients are often mechanically ventilated and thereby at risk for ventilator-induced lung injury (VILI) which influences their outcome. VILI develops due to the detrimental local and systemic pro-inflammatory response, which is triggered by mechanical ventilation. We aimed to investigate whether dysregulation of the gut microbiome may impact the pulmonary inflammatory response to mechanical ventilation and the development of VILI.

Methods:

The gut microbiome was depleted in mice during a 6 week enteral antibiotic combination therapy. Control mice were equally housed throughout this period. After 6 weeks VILI was induced by high tidal volume ventilation (34 ml/kg) for 4 hours. Control groups of mice ventilated with low tidal volume ventilation and non-ventilated mice were analyzed accordingly. Lung function, oxygenation capacity, pulmonary vascular leakage, macroscopic assessment of lung injury, leukocyte and lymphocyte differentiation in lung and blood were assessed.

Results:

Compared to controls, mice lacking an intact gut microbiome developed a significantly higher extend of VILI reflected by increased pulmonary permeability, decreased pulmonary compliance and aggravated macroscopically assed pulmonary injury. This effect was not mediated by the cellular inflammatory response to mechanical ventilation.

Conclusion:

Disruption of the gut microbiome augmented the development of VILI in mice, which may be of relevance for critically ill patients receiving broad-spectrum antibiotics or SDD.