Bacterial Signatures of Paediatric Respiratory Disease: An Individual Participant Data Meta-Analysis

Abstract

Introduction: The airway microbiota has been linked to specific paediatric respiratory diseases, but studies are often small. It remains unclear whether particular bacteria are associated with a given disease, or if a more general, non-specific microbiota association with disease exists, as suggested for the gut. We investigated overarching patterns of bacterial association with acute and chronic paediatric respiratory disease in an individual participant data (IPD) meta-analysis of 16S rRNA gene sequences from published respiratory microbiota studies. Methods: We obtained raw microbiota data from public repositories or via communication with corresponding authors. Cross-sectional analyses of the paediatric (<18 years) microbiota in acute and chronic respiratory conditions, with >10 case subjects were included. Sequence data were processed using a uniform bioinformatics pipeline, removing a potentially substantial source of variation. Microbiota differences across diagnoses were assessed using alpha- and beta-diversity approaches, machine learning, and biomarker analyses. Results: We ultimately included 20 studies containing individual data from 2624 children. Disease was associated with lower bacterial diversity in nasal and lower airway samples and higher relative abundances of specific nasal taxa including Streptococcus and Haemophilus . Machine learning success in assigning samples to diagnostic groupings varied with anatomical site, with positive predictive value and sensitivity ranging from 43 to 100 and 8 to 99%, respectively. Conclusion: IPD meta-analysis of the respiratory microbiota across multiple diseases allowed identification of a non-specific disease association which cannot be recognised by studying a single disease. Whilst imperfect, machine learning offers promise as a potential additional tool to aid clinical diagnosis. (Copyright © 2021 Broderick, Waite, Marsh, Camargo, Cardenas, Chang, Cookson, Cuthbertson, Dai, Everard, Gervaix, Harris, Hasegawa, Hoffman, Hong, Josset, Kelly, Kim, Kong, Li, Mansbach, Mejias, O’Toole, Paalanen, Pérez-Losada, Pettigrew, Pichon, Ramilo, Ruokolainen, Sakwinska, Seed, van der Gast, Wagner, Yi, Zemanick, Zheng, Pillarisetti and Taylor.)eCollection. Cited Medium: Print. NLM ISO Abbr: Front Microbiol. PubMed Central ID: PMC8733647. Linked References: PeerJ. 2018 Apr 2;6:e4600. (PMID: 29629248); Appl Environ Microbiol. 2009 Dec;75(23):7537-41. (PMID: 19801464); Lancet Respir Med. 2018 Jun;6(6):461-471. (PMID: 29778403); Cell Host Microbe. 2015 May 13;17(5):704-15. (PMID: 25865368); Am J Respir Crit Care Med. 2014 Dec 1;190(11):1283-92. (PMID: 25329446); PLoS One. 2017 Dec 27;12(12):e0190075. (PMID: 29281698); BMC Bioinformatics. 2021 May 25;22(1):265. (PMID: 34034646); Environ Microbiol. 2017 Apr;19(4):1450-1462. (PMID: 28078754); Nat Commun. 2017 Dec 5;8(1):1784. 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