Faculty Bibliography

Oral flora are frequently found in normal individuals' lungs without known harm. We hypothesize that a lung microbiome enriched by oral taxa would be associated with a higher degree of inflammation. We studied 29 asymptomatic subjects (9 nonsmokers and 20 smokers) with preserved lung function. Nasal bronchoscopy was performed with two separate bronchoscopes to retrieve supraglotic and lower airway samples. Bronchoalveolar lavage (BAL) cell count, BAL cytokines (Luminex), and exhaled nitric oxide defined pulmonary inflammation. Quantitative PCR measured 16S rRNA gene concentration and 454 sequences defined the microbiome. Supraglotic samples had the highest 16S rRNA concentration, BAL was intermediate, and saline used for the BAL had the lowest concentration. Nonsmokers and smokers were similar in BAL cell differential and lung microbiome. BAL samples segregated into two distinct groups that we called pneumotypes. Pneumotype background predominant taxa (pneumotypeBPT) was similar to the saline background in rDNA concentration or microbial community. Pneumotype supraglotic-characteristic taxa (pneumotypeSCT) has higher rDNA concentration and high relative abundance of SCT, such as Prevotella and Veillonella. PneumotypeSCT was associated with multiple measures of lung inflammation, including higher BAL neutrophils, IL-8, and levels of exhaled nitric oxide. PneumotypeSCT also had higher BAL lymphocytes and fractalkine, a chemokine that correlates with T helper type 17:T regulatory cell ratio in the BAL. These data suggest that a pneumotype with high relative abundance of supraglotic bacteria, such as Prevotella and Veillonella, is associated with increased innate and cellular inflammation.

The development of culture-independent techniques has revolutionized our understanding of how our human cells interact with the even greater number of microbial inhabitants of our bodies. As part of this revolution, data are increasingly challenging the old dogma that in health, the lung mucosa is sterile. To understand how the lung microbiome may play a role in human health, we identified five major questions for lung microbiome research: (1) Is the lung sterile? (2) Is there a unique core microbiome in the lung? (3) How dynamic are the microbial populations? (4) How do pulmonary immune responses affect microbiome composition? and (5) Are the lungs influenced by the intestinal immune responses to the gut microbiome? From birth, we are exposed to continuous microbial challenges that shape our microbiome. In our changing environment, perturbation of the gut microbiome affects both human health and disease. With widespread antibiotic use, the ancient microbes that formerly resided within us are being lost, for example, Helicobacter pylori in the stomach. Animal models show that antibiotic exposure in early life has developmental consequences. Considering the potential effects of this altered microbiome on pulmonary responses will be critical for future investigations.