Cystic fibrosis (CF) is a fatal genetic disease characterized by chronic lung infections due to aberrant mucus production and the inability to clear invading pathogens. The traditional view that CF infections are caused by a single pathogen has been replaced by the realization that the CF lung usually is colonized by a complex community of bacteria, fungi and viruses. To help unravel the complex interplay between the CF lung environment and the infecting microbial community, we developed a

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... nity metabolic model comprised of the 17 most abundant bacterial taxa, which account for >95% of reads across samples, from three published studies in which 75 sputum samples from 46 adult CF patients were analyzed by 16S rRNA gene sequencing. The community model was able to correctly predict high abundances of the rare pathogens Enterobacteriaceae, Burkholderia and Achromobacter in three patients whose polymicrobial infections were dominated by these pathogens. With these three pathogens were removed, the model correctly predicted that the remaining 43 patients would be dominated by Pseudomonas and/or Streptococcus. This dominance was predicted to be driven by relatively high monoculture growth rates of Pseudomonas and Streptococcus as well as their ability to efficiently consume amino acids, organic acids and alcohols secreted by other community members. Sample-by-sample heterogeneity of community composition could be qualitatively captured through random variation of the simulated metabolic environment, suggesting that experimental studies directly linking CF lung metabolomics and 16S sequencing could provide important insights into disease progression and treatment efficacy.