Sputum microbiome profiling in COPD: beyond singular pathogen detection.

Culture-independent microbial sequencing techniques have revealed that the respiratory tract harbours a complex microbiome not detectable by conventional culturing methods. The contribution of the microbiome to chronic obstructive pulmonary disease (COPD) pathobiology and the potential for microbiome-based clinical biomarkers in COPD are still in the early phases of investigation. Sputum is an easily obtainable sample and has provided a wealth of information on COPD pathobiology, and thus has been a preferred sample type for microbiome studies. Although the sputum microbiome likely reflects the respiratory microbiome only in part, there is increasing evidence that microbial community structure and diversity are associated with disease severity and clinical outcomes, both in stable COPD and during the exacerbations. Current evidence has been limited to mainly cross-sectional studies using 16S rRNA gene sequencing, attempting to answer the question 'who is there?' Longitudinal studies using standardised protocols are needed to answer outstanding questions including differences between sputum sampling techniques. Further, with advancing technologies, microbiome studies are shifting beyond the examination of the 16S rRNA gene, to include whole metagenome and metatranscriptome sequencing, as well as metabolome characterisation. Despite being technically more challenging, whole-genome profiling and metabolomics can address the questions 'what can they do?' and 'what are they doing?' This review provides an overview of the basic principles of high-throughput microbiome sequencing techniques, current literature on sputum microbiome profiling in COPD, and a discussion of the associated limitations and future perspectives.

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© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

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Competing interests: SC reports personal fees from AstraZeneca, personal fees from GlaxoSmithKline, personal fees from Amgen, personal fees from Glenmark, personal fees from Sunovion, personal fees and non-financial support from Genentech, non-financial support from Medimmune, personal fees from UpToDate, outside the submitted work. CB reports grants and personal fees from GSK, grants and personal fees from AZ/MedImmune, grants and personal fees from Novartis, grants and personal fees from Chiesi, grants from Roche/Genentech, grants and personal fees from Mologic, grants and personal fees from Gossamer, grants and personal fees from BI, grants and personal fees from 4DPharma, personal fees from Sanofi, personal fees from Regeneron, personal fees from Theravance, outside the submitted work. JR reports personal fees from IDbyDNA, from null, outside the submitted work. HAMK reports an unrestricted research grant, and fees for participation in advisory boards from GlaxoSmithKline, the sponsor of this study as well as from Boehringer Ingelheim, and Novartis. He also reports fees advisory board participation for AstraZeneca and Chiesi. All above paid to his institution,outside the submitted work. BD, AF and MvdB have nothing to disclose