Bile acid-induced lung injury: update of reverse translational biology

The presence of bile acids in lung tissue is associated with some clinical features observed in various medical specialties, but it took time to understand that these are due to a "bile acid-induced lung injury" since specific translational studies and cross-disciplinary awareness were lacking. We used a reverse translational approach to update and summarize the current knowledge about the mechanisms of bile acid-induced lung injury. This has been done in a cross-disciplinary fashion since these conditions may occur in patients of various ages and in different medical fields. We here define these clinical conditions, then we review the physiopathology of these conditions and the animal models used to mimic them, and, finally, their pathobiology. Mechanisms of bile acid-induced lung injury have been partially clarified over time and are represented by 1) the interaction with secretory phospholipase A2 pathway, 2) the effect on surfactant function and structure, 3) the biological effects on inflammation and local immunity, and 4) the direct cellular toxicity. These mechanisms are schematically illustrated and histological comparisons between acute respiratory distress syndrome (ARDS) induced by bile acids and other triggers are also provided. Based on these mechanisms, we propose possible direct therapeutic applications and, finally, we discuss further research steps to improve the understanding of processes that generate pathological clinical conditions.