Sputum metagenomics of people with bronchiectasis

<bold>Background:</bold> Disease progression of bronchiectasis arises from a "vicious vortex" of airway dysfunction, structural damage, inflammation and persistent infection. Our study examined the sputum microbiota of people with non-CF bronchiectasis up to the species level. <bold>Objective:</bold> The global objective of our ongoing studies is to define microbial dysbiosis in chronic lung diseases. This particular study addresses the question whether specific airway metagenome signatures differentiate people with bronchiectasis from healthy individuals. <bold>Methods:</bold> We performed shotgun metagenomic sequencing of sputum samples from healthy nonsmokers (n=88) and people with bronchiectasis (enrolled through EMBARC, n=101). Fragment libraries were sequenced on an Illumina NextSeq plattform. Quality filtering, alignment of the short reads to a reference database and normalisation were performed by our in-house developed pipeline Wochenende. <bold>Results:</bold> The individual metagenomes of people with bronchiectasis clustered by the absence or presence of <italic>H. influenzae</italic> and <italic>P. aeruginosa</italic>, constituting the two most frequently detected pathogens. Alpha diversity measures were significantly decreased in severe bronchiectasis. Comparison with the sputum metagenome of healthy nonsmokers revealed a gradient of depletion of commensal taxa in bronchiectasis. Common inhabitants of the respiratory tract of healthy subjects including <italic>Fusobacterium periodonticum</italic>, <italic>Eubacterium sulci</italic> and <italic>Neisseria subflava</italic> were rarely detectable in bronchiectasis, even in the absence of any respiratory pathogen. <bold>Conclusion:</bold> We hypothesize that the suppression of indicator commensal species associated with lung health is diagnostic for microbial dysbiosis in people with bronchiectasis.