Medical Research: What is the background for this study?
Dr. Huang: Asthma is a disease with many different clinical manifestations, and it is likely that multiple mechanisms play a role in asthma. Understanding the biological processes that contribute to this heterogeneity is an important goal of current translational research in asthma. One hypothesis that dates back several decades is whether asthma, at least in some forms, is linked to chronic airway infection or colonization by particular species of bacteria. Results of early investigations in this regard were mixed, in part due to reliance on less sensitive methods to detect bacterial infection, but a new spin on this hypothesis has emerged in recent years. This stems from the technological advances that now enable one to molecularly profile all bacteria present in a sample, such as via sequence analysis of conserved bacterial genes (such as that for 16S ribosomal RNA). 16S rRNA-based methods are now commonly used to profile bacterial microbiota in a variety of human niches, including in studies of respiratory disease.
Prior to our current study, a few investigations had shown that the lower respiratory microbiome in adult asthmatics differs in bacterial composition (i.e. the types and relative abundance of bacteria present), compared to healthy controls. In a previous study of patients with mild-moderate asthma, we also had found that clinical features of asthma, such as bronchial hyper-responsiveness, were associated with increased abundance of specific bacterial groups. However, whether similar relationships between clinical features and the microbiome exist in severe asthma was unknown, which we addressed in the current study.
Medical Research: What are the main findings?
Dr. Huang: We evaluated bronchial epithelial brushings from 40 severe asthma patients for analysis of the bacterial microbiome. The bacterial community profiles ultimately obtained were analyzed for relationships to clinical and inflammatory features, extensively characterized in these patients. We found several significant associations between the abundance of specific bacterial communities and disease-related features in this cohort, including asthma control, co-morbid obesity, and bronchial epithelial expression of genes related to steroid-response and Th17 inflammation. Several of these findings dovetailed. For example, members of the Proteobacteria phylum, which includes many potential respiratory pathogens, were strongly associated with worse asthma control as well as expression of Th17-related genes. By contrast, greater abundance of Actinobacteria members was associated with both better asthma control and increased expression of FKBP5, a steroid-responsive gene, suggesting that particular organisms in this phylum may be a microbial marker of steroid effectiveness.
Finally, a somewhat surprising result was the absence of any significant associations between the bronchial bacterial microbiome and markers related to type 2 inflammation. In fact measures of bacterial burden correlated negatively with airway biopsy eosinophil numbers. While further studies are warranted, we speculate that one possibility is whether other non-bacterial microbiota may play a role in perpetuating type 2 inflammation in severe asthma.
Medical Research: What should clinicians and patients take away from your report?
Dr. Huang: Microbial dysbiosis (i.e. microbial imbalance) is present in the lower airways of severe asthmatics and linked to certain clinical features in this disease.
These findings suggest that differences in airway abundance of particular bacterial groups are associated with different clinical outcomes and patterns of airway inflammation.
However, since severe asthma patients typically are on higher doses of inhaled corticosteroids, the extent to which certain observations are influenced by potential effects of steroids is difficult to dissect. Therefore, findings from this clinical study should inform the design of future investigations that can delve into mechanisms underlying the very interesting relationships we observed.
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Yvonne J. Huang, MD (2015). Abnormal Lung Microbiome Linked To Severe Asthma