Background: Ecological networking and in vitro studies have predicted that anaerobic, mucus-degrading bacteria are keystone species in cystic fibrosis (CF) microbiomes by sustaining the growth of canonical CF pathogens. Here, a multi-omics approach was deployed to test this hypothesis in vivo and in real time during a transition in antibiotic therapy of a CF patient with a hypervariable lung function phenotype .
Results: Quantitative meta-omics and community culturing demonstrated that the use of a non-traditional clindamycin therapy targeting gram-positives and gram-negative anaerobes re-structured the entire CF microbial community. During rapid lung function loss, when the patient was off antibiotics, the microbial community was dominated by anaerobic mucus-degrading Streptococcus sp., Veilonella sp., and Prevotella sp. that produced fermentation gas and led to the accumulation of fermentation products in sputum. The rise of anaerobes was followed within 6 days by an increase in Pseudomonas aeruginosa transcripts encoding the acquisition of fermentation products from anaerobes and the production of virulence factors. The initiation of clindamycin treatment reduced the fermentation and the abundance of anaerobes. Clindamycin also lowered the abundance and transcription of P. aeruginosa, which is resistant to this antibiotic. The treatment stabilized the patient’s lung function and improved respiratory health for two months, lengthening by a factor of four the between-hospitalization time for this patient.
Conclusions: The results presented here show that killing anaerobes, the weakest link in the community in terms of antibiotic resistance, effectively limited the growth of classic CF pathogen by disrupting community cross-feeding. The role that anaerobic, mucus-degrading bacteria played in structuring the CF microbiome corroborates in vivo their position as keystone bacteria, with high impact on community function despite lower relative abundances.