Frontiers in Microbiology (Dec 2021)
Bacterial Signatures of Paediatric Respiratory Disease: An Individual Participant Data Meta-Analysis
- David T. J. Broderick,
- David W. Waite,
- Robyn L. Marsh,
- Carlos A. Camargo,
- Carlos A. Camargo,
- Carlos A. Camargo,
- Paul Cardenas,
- Anne B. Chang,
- Anne B. Chang,
- Anne B. Chang,
- William O. C. Cookson,
- William O. C. Cookson,
- Leah Cuthbertson,
- Wenkui Dai,
- Mark L. Everard,
- Alain Gervaix,
- J. Kirk Harris,
- Kohei Hasegawa,
- Kohei Hasegawa,
- Kohei Hasegawa,
- Lucas R. Hoffman,
- Lucas R. Hoffman,
- Soo-Jong Hong,
- Laurence Josset,
- Matthew S. Kelly,
- Bong-Soo Kim,
- Yong Kong,
- Shuai C. Li,
- Shuai C. Li,
- Jonathan M. Mansbach,
- Jonathan M. Mansbach,
- Asuncion Mejias,
- George A. O’Toole,
- Laura Paalanen,
- Marcos Pérez-Losada,
- Marcos Pérez-Losada,
- Melinda M. Pettigrew,
- Maxime Pichon,
- Maxime Pichon,
- Octavio Ramilo,
- Lasse Ruokolainen,
- Olga Sakwinska,
- Patrick C. Seed,
- Christopher J. van der Gast,
- Brandie D. Wagner,
- Hana Yi,
- Edith T. Zemanick,
- Yuejie Zheng,
- Naveen Pillarisetti,
- Michael W. Taylor
Affiliations
- David T. J. Broderick
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
- David W. Waite
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
- Robyn L. Marsh
- Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
- Carlos A. Camargo
- Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, United States
- Carlos A. Camargo
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Carlos A. Camargo
- Harvard Medical School, Boston, MA, United States
- Paul Cardenas
- Colegio de Ciencias Biológicas y Ambientales, Instituto de Microbiología, Universidad San Francisco de Quito, Quito, Ecuador
- Anne B. Chang
- Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
- Anne B. Chang
- Department of Respiratory and Sleep Medicine, Queensland Children’s Hospital, Brisbane, QLD, Australia
- Anne B. Chang
- Australian Centre for Health Services Innovation, Queensland University of Technology, Brisbane, QLD, Australia
- William O. C. Cookson
- National Heart and Lung Institute, Imperial College London, London, United Kingdom
- William O. C. Cookson
- 0Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
- Leah Cuthbertson
- 0Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
- Wenkui Dai
- 1Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, China
- Mark L. Everard
- 2School of Medicine, University of Western Australia, Perth, WA, Australia
- Alain Gervaix
- 3Department of Pediatrics, Gynecology and Obstetrics, Faculty of Medicine, University Hospitals of Geneva, Geneva, Switzerland
- J. Kirk Harris
- 4Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, United States
- Kohei Hasegawa
- Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, United States
- Kohei Hasegawa
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Kohei Hasegawa
- Harvard Medical School, Boston, MA, United States
- Lucas R. Hoffman
- 5Seattle Children’s Hospital, Seattle, WA, United States
- Lucas R. Hoffman
- 6Department of Pediatrics and Microbiology, University of Washington, Seattle, WA, United States
- Soo-Jong Hong
- 7Department of Pediatrics, Childhood Asthma Atopy Center, Humidifier Disinfectant Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
- Laurence Josset
- 8Hospices Civils de Lyon, Lyon, France
- Matthew S. Kelly
- 9Division of Pediatric Infectious Diseases, Duke University, Durham, NC, United States
- Bong-Soo Kim
- 0Department of Life Science, Multidisciplinary Genome Institute, Hallym University, Chuncheon, South Korea
- Yong Kong
- 1Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, United States
- Shuai C. Li
- 2Department of Computer Science, City University of Hong Kong, Kowloon, Hong Kong SAR, China
- Shuai C. Li
- 3Department of Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR, China
- Jonathan M. Mansbach
- Harvard Medical School, Boston, MA, United States
- Jonathan M. Mansbach
- 4Department of Pediatrics, Boston Children’s Hospital, Boston, MA, United States
- Asuncion Mejias
- 5Division of Pediatric Infectious Diseases, Department of Pediatrics, Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children’s Hospital, The Ohio State University College of Medicine, Columbus, OH, United States
- George A. O’Toole
- 6Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Laura Paalanen
- 7Finnish Institute for Health and Welfare (THL), Helsinki, Finland
- Marcos Pérez-Losada
- 8Department of Biostatistics and Bioinformatics, Computational Biology Institute, Milken Institute School of Public Health, George Washington University, Washington, DC, United States
- Marcos Pérez-Losada
- 9CIBIO-InBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, Vairão, Portugal
- Melinda M. Pettigrew
- 0Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, United States
- Maxime Pichon
- 1CHU Poitiers, Infectious Agents Department, Poitiers, France
- Maxime Pichon
- 2University of Poitiers, INSERM U1070, Poitiers, France
- Octavio Ramilo
- 5Division of Pediatric Infectious Diseases, Department of Pediatrics, Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children’s Hospital, The Ohio State University College of Medicine, Columbus, OH, United States
- Lasse Ruokolainen
- 3Department of Biosciences, University of Helsinki, Helsinki, Finland
- Olga Sakwinska
- 4Nestlé Research, Lausanne, Switzerland
- Patrick C. Seed
- 5Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
- Christopher J. van der Gast
- 6Department of Life Sciences, Manchester Metropolitan University, Manchester, United Kingdom
- Brandie D. Wagner
- 7Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado, Aurora, Aurora, CO, United States
- Hana Yi
- 8School of Biosystem and Biomedical Science, Korea University, Seoul, South Korea
- Edith T. Zemanick
- 4Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, United States
- Yuejie Zheng
- 9Shenzhen Children’s Hospital, Shenzhen, China
- Naveen Pillarisetti
- 0Starship Children’s Hospital, Auckland, New Zealand
- Michael W. Taylor
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
- DOI
- https://doi.org/10.3389/fmicb.2021.711134
- Journal volume & issue
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Vol. 12
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.
Keywords
- microbiota (16S)
- respiratory tract
- respiratory infection
- paediatrics
- meta-analysis
- individual participant data (IPD) meta-analysis