Intercepting the bile aspiration paradigm: Innovative intervention for Chronic Respiratory Disease
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Chronic respiratory infections associated with lung disease are a major cause of global morbidity and mortality. However, despite concerted global research efforts current treatment strategies remain extremely limited, particularly where chronic pathogens adopt the biofilm lifestyle, becoming intrinsically resistant to antibiotic therapy. We have shown that the aspiration of bile acids into the lungs correlates with a significant [Mann–Whitney U test p \ 0.05)] reduction in lung microbial biodiversity in paediatric cystic fibrosis (CF) patients, characterised by the emergence of dominant Proteobacterial pathogens. This is consistent with our in vitro studies which have shown that bile acids trigger the establishment of dominant chronic biofilm forming microbial species, particularly Pseudomonas aeruginosa. Bile acids also triggered production of the IL-6 pro-inflammatory cytokine in IB3-1 lung epithelial cells, while suppressing the key immune and hypoxic response regulator HIF-1. Further supported by evidence from studies on gastroesophageal reflux (GER), a primary driver of bile aspiration, these data strongly support the hypothesis that bile acids in the lungs are a major factor leading to reduced lung function in respiratory disease. Understanding the aspirated bile—chronic infection/inflammation paradigm will provide a real opportunity to develop innovative interventionalist therapies that target aspiration, thus resolving the chronic pathophysiology of respiratory disease.
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