Microbial content versus microbial interaction: the impact of medications on CF airway microbial ecosystems.

BACKGROUND: The airways of people with cystic fibrosis (pwCF) are often colonized by a variety of different microbes. Although much effort has been put into cataloguing the impact of medication on the identities and abundances of these microbes, far less has been directed towards examining this from an ecological perspective, i.e., examining how medications affect the network and types of interactions between microbes. METHODS: In the current work, we generated an ecological model of the CF airway microbiome and examined how medications affect interactions between co-habiting airway microbiota in six pwCF. Ecological interactions were inferred from a generalized Lotka-Volterra model, and the impact of medications was determined by principal component(s) regression analysis. RESULTS: For the majority of the subjects studied, antimicrobial interventions had relatively little impact on the CF airway microbial ecology, and even appeared to stabilize ecological interactions between the microbiota. However, the microbial ecosystem in some individuals was more sensitive to external perturbations. More surprisingly, we found that some non-antimicrobial medications, and also certain carriers and excipients affect the ecosystem. CONCLUSIONS: Medications affect the ecology of the CF airway microbiota. These impacts appear to be very patient-specific. We also note that some nominally non-bioactive ingredients in medications can also potentially impact the CF airway ecosystem. Our data highlight the importance of collecting patient-specific data and in employing suitable computational frameworks for disentangling medication-microbiota interactions in vivo.