Autophagy suppression plays a role in parenteral nutrition-associated lung injury

Abstract

Background & aims: The long-term usage of parenteral nutrition (PN) is associated with the increased incidence of pneumonia. Few studies have focused on the pathogenesis of PN-associated lung injury (PNLI). Previous studies have found that autophagy suppression may be an important mechanism for PN-associated complications. The present study aimed to investigate the effect of PN on lung barrier impairment and its association with autophagy.

Methods: We retrospectively identified intestinal failure patients admitted to a clinical nutrition service center to determine the morbidity of hospital-acquired pneumonia (HAP) and its association with PN. In animal studies, we established the PNLI mouse model to measure severity of lung injury, lung barrier, pulmonary microbiota in bronchoalveolar fluid (BALF), levels of autophagy and apoptosis, and the inflammatory signaling pathway.

Result: Among the 259 patients, 37 (14.3%) patients developed HAP. Multivariate analysis revealed that prolonged PN was an independent predictor for HAP. In animal studies, we found that PN impaired the lung barrier and disturbed pulmonary microbiota homeostasis. The abundance of Actinomycetes and Firmicutes phyla in BALF were significantly increased, while the Bacteroidetes phylum decreased. Bacterial translocations in the lung were observed by fluorescence in situ hybridization. PN caused autophagy suppression and activated the apoptosis level and inflammatory HMGB1/RAGE/NF-kB signaling pathway. The intervention of exogenous rapamycin can attenuate the impairment of the lung barrier, reduce apoptosis and inhibit inflammatory signaling by upregulation of autophagy.

Conclusion: PN had a damaging effect on the lung barrier, disturbed pulmonary microbiota homeostasis, and induced bacterial translocation. Autophagy suppression might be a crucial mechanism in inducing PNLI.

Keywords: Autophagy; Hospital-acquired pneumonia; Intestinal failure; Lung barrier impairment; Parenteral nutrition; Parenteral nutrition-associated lung injury.