Analysis of Changes in Diversity and Abundance of the Microbial Community in a Cystic Fibrosis Patient over a Multiyear Period

Abstract

The evolution of pulmonary disease in cystic fibrosis (CF) usually begins when bacteria get trapped in mucus in the lungs and become established as a chronic infection. While most CF patients experience periods of stability, pulmonary exacerbations (PEs) can occur multiple times per year and result in permanent damage to the lungs. Little is known of the shift from a period of stability to a PE, but this shift is likely to be attributed to changes in the bacterial community. Here, we identified changes in the lung microbiota to determine if they reflect patient health, indicate the onset of exacerbations, or are related to antibiotic treatment. In contrast to most bacterial studies on CF, we collected weekly samples from an adult CF patient over a period of 3 years and performed quantitative PCR (qPCR) and Illumina sequencing on those samples. While many DNA-based studies have shown the CF microbiota to be relatively stable, we observed an increase in the total bacterial abundance over time (P< 0.001), while the number of different taxa (bacterial richness) and the number of different taxa and their abundances (diversity) significantly decreased over time (P< 0.03), which was likely due to repeated antibiotic exposure. Using genus-specific primers with qPCR, we observed an increase in the abundance ofBurkholderia multivorans, a CF-associated pathogen, prior to the occurrence of a PE (P= 0.006). Combining these DNA-based techniques with frequent sampling identified a potential initiator for exacerbations and described a response of the CF microbiota to time and antibiotic treatment not observed in previous CF microbiota studies.