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Aspirated bile: a major host trigger modulating respiratory pathogen colonisation in cystic fibrosis patients
Abstract:
Chronic respiratory infections are a leading global cause of morbidity and mortality. However, the molecular triggers that cause respiratory pathogens to adopt persistent and often untreatable lifestyles during infection remain largely uncharacterised. Recently, bile aspiration caused by gastro-oesophageal reflux (GOR) has emerged as a significant complication associated with respiratory disease, and cystic fibrosis (CF) in particular. Based on our previous finding that the physiological concentrations of bile influence respiratory pathogens towards a chronic lifestyle in vitro, we investigated the impact of bile aspiration on the lung microbiome of respiratory patients. Sputum samples (n = 25) obtained from a cohort of paediatric CF patients were profiled for the presence of bile acids using high-resolution liquid chromatography-mass spectrometry (LC-MS). Pyrosequencing was performed on a set of ten DNA samples that were isolated from bile aspirating (n = 5) and non-bile aspirating (n = 5) patients. Both denaturing gradient gel electrophoresis (DGGE) and pyrosequencing revealed significantly reduced biodiversity and richness in the sputum samples from bile aspirating patients when compared with non-aspirating patients. Families and genera associated with the pervasive CF microbiome dominated aspirating patients, while bacteria associated with the healthy lung were most abundant in non-aspirating patients. Bile aspiration linked to GOR is emerging as a major host trigger of chronic bacterial infections. The markedly reduced biodiversity and increased colonisation by dominant proteobacterial CF-associated pathogens observed in the sputum of bile aspirating patients suggest that bile may play a major role in disease progression in CF and other respiratory diseases.
Insights
Bile aspiration from acid reflux significantly reduces lung microbiome diversity in cystic fibrosis patients. This shift promotes chronic infections by promoting harmful bacteria, impacting disease progression.
Area of Science:
- Microbiology
- Pulmonology
- Gastroenterology
Background:
- Chronic respiratory infections are a major cause of illness and death globally.
- The triggers for persistent, untreatable respiratory infections are poorly understood.
- Bile aspiration due to gastro-oesophageal reflux (GOR) is increasingly linked to respiratory diseases, especially cystic fibrosis (CF).
Purpose of the Study:
- To investigate the impact of bile aspiration on the lung microbiome in pediatric CF patients.
- To determine if bile influences the microbial community structure in the lungs.
Main Methods:
- Sputum samples from 25 pediatric CF patients were analyzed for bile acids using liquid chromatography-mass spectrometry (LC-MS).
- DNA from 10 patients (5 bile aspirating, 5 non-bile aspirating) was analyzed using pyrosequencing and denaturing gradient gel electrophoresis (DGGE).
Main Results:
- Bile aspirating patients showed significantly reduced lung microbiome biodiversity and richness compared to non-aspirating patients.
- The lungs of bile aspirating patients were dominated by CF-associated bacteria, while non-aspirating patients had more healthy lung-associated bacteria.
- Bile acids were detected in the sputum of bile aspirating patients.
Conclusions:
- Bile aspiration, linked to GOR, acts as a significant host trigger for chronic bacterial infections in the lungs.
- Reduced lung biodiversity and increased colonization by CF-associated pathogens in bile aspirating patients suggest bile plays a key role in CF disease progression.
- These findings highlight bile aspiration as a critical factor in the development and progression of respiratory diseases like CF.
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