Bile Acid Aspiration Associated With Lung Chemical Profile Linked to Other Biomarkers of Injury After Lung Transplantation

Abstract

Aspiration of gastrointestinal contents has been linked to worse outcomes following lung transplantation but uncertainty exists about underlying mechanisms. We applied high-resolution metabolomics of bronchoalveolar lavage fluid (BALF) in patients with episodic aspiration (defined by bile acids in the BALF) to identify potential metabolic changes associated with aspiration. Paired samples, one with bile acids and another without, from 29 stable lung transplant patients were studied. Liquid chromatography coupled to high-resolution mass spectroscopy was used to interrogate metabolomic contents of these samples. Data were obtained for 7068 ions representing intermediary metabolites, environmental agents and chemicals associated with microbial colonization. A substantial number (2302) differed between bile acid positive and negative samples when analyzed by false discovery rate at q=0.01. These included pathways associated with microbial metabolism. Hierarchical cluster analysis defined clusters of chemicals associated with bile acid aspiration that were correlated to previously reported biomarkers of lung injury including T cell granzyme B level and the chemoattractants CXCL9 and CXCL10. These data specifically link bile acids presence in lung allografts to inflammatory pathways known to segregate with worsening allograft outcome, and provide additional mechanistic insight into the association between reflux and lung allograft injury. This study shows that distinct biochemical patterns are found in the lung lavages of transplant patients depending on the presence or absence of bile acids, and links these biochemical patterns to other biomarkers of lung injury.