Meta-analysis of sputum microbiome studies identifies airway disease-specific taxonomic and functional signatures

Introduction. Studying taxonomic and functional signatures of respiratory microbiomes provide a better understanding of airway diseases. Gap Statement . Several human airway metagenomics studies have identified taxonomic and functional features restricted to a single disease condition and the findings are not comparable across airway diseases due to use of different samples, NGS platforms, and bioinformatics databases and tools. Aim. To study the microbial taxonomic and functional components of sputum microbiome across airway diseases and healthy smokers. Methodology. Here, 57 whole metagenome shotgun sequencing (WMSS) runs coming from the sputum of five airway diseases: asthma, bronchiectasis, chronic obstructive pulmonary diseases (COPD), cystic fibrosis (CF), tuberculosis (TB), and healthy smokers as the control were reanalysed using a common WMSS analysis pipeline. Results. Shannon’s index (alpha diversity) of the healthy smoker group was the highest among all. The beta diversity showed that the sputum microbiome is distinct in major airway diseases such as asthma, COPD and cystic fibrosis. The microbial composition based on differential analysis showed that there are specific markers for each airway disease like Acinetobacter bereziniae as a marker for COPD and Achromobacter xylosoxidans as a marker of cystic fibrosis. Pathways and metabolites identified from the sputum microbiome of these five diseases and healthy smokers also show specific markers. ‘ppGpp biosynthesis’ and ‘purine ribonucleosides degradation’ pathways were identified as differential markers for bronchiectasis and COPD. In this meta-analysis, besides bacteria kingdom, Aspergillus fumigatus was detected in asthma and COPD, and Roseolovirus human betaherpesvirus 7 was detected in COPD. Our analysis showed that the majority of the gene families specific to the drug-resistant associated genes were detected from opportunistic pathogens across all the groups. Conclusion. In summary, the specific species in the sputum of airway diseases along with the microbial features like specific gene families, pathways, and metabolites were identified which can be explored for better diagnosis and therapy.