Anaerobic bacteria cultured from cystic fibrosis airways correlate to milder disease: a multisite study

Abstract

Anaerobic and aerobic bacteria were quantitated in respiratory samples across three cystic fibrosis (CF) centres using extended culture methods. Subjects aged 1-69 years who were clinically stable provided sputum (n=200) or bronchoalveolar lavage (n=55). 18 anaerobic and 39 aerobic genera were cultured from 59% and 95% of samples, respectively; 16 out of 57 genera had a ≥5% prevalence across centres.Analyses of microbial communities using co-occurrence networks in sputum samples showed groupings of oral, including anaerobic, bacteria, whereas typical CF pathogens formed distinct entities. Pseudomonas was associated with worse nutrition and F508del genotype, whereas anaerobe prevalence was positively associated with pancreatic sufficiency, better nutrition and better lung function. A higher total anaerobe/total aerobe CFU ratio was associated with pancreatic sufficiency and better nutrition. Subjects grouped by factor analysis who had relative dominance of anaerobes over aerobes had milder disease compared with a Pseudomonas-dominated group with similar proportions of subjects that were homozygous for F508del.In summary, anaerobic bacteria occurred at an early age. In sputum-producing subjects anaerobic bacteria were associated with milder disease, suggesting that targeted eradication of anaerobes may not be warranted in sputum-producing CF subjects.

Figure 1A:. Richness by age groups across all sites and sample types

Richness defined as number of anaerobic and aerobic genera detected at any CFU per sample and did not differ between the age groups within sample types.

Figure 1B:. Prevalence of most frequently cultured bacteria by age groups across all sites and sample types.

Prevalence for most prevalent bacteria are shown by age groups/range in years. The number of samples for each group is provided in parenthesis. Only BAL samples are included in subjects <6 years, as indicated by the vertical line.

Figure 2:. Prevalence as percent of subjects with any CFU/g sputum for a) Anaerobes, b) Haemophilus, c) Staphylococcus, and d) Pseudomonas in sputum and their association with clinical characteristics

BMI are 1 - poor nutritional status; 2 - adequate; 3 - well-nourished. Categories for FEV1 are 1: <40% predicted; 2: 40-80%; 3: >80%. Numbers per category are given as percentage of subjects positive for this characteristic. Comparisons are by Mantel-Haenzel mean score chi-square test stratified by site.

Figure 3:. Bacterial co-occurrence network between genera detected by extended microbial culture.

The sixteen genera detected in ≥5% of sputum samples are contained within the network. Co-occurring microbial taxa are shown with nodes (circles) denoting a particular taxon within the network and each line (edge) a significant co-occurrence relationship (Spearman's rank correlation coefficient for positive correlations (blue lines); adjusted p-value <0.05 [FDR correction]). The size of the corresponding nodes demonstrates the relative proportion of each genera within the current study and the thickness of edges represents the strength of the corresponding associations.