Airway Microbiota Dynamics Uncover a Critical Window for Interplay of Pathogenic Bacteria and Allergy in Childhood Respiratory Disease

Shu Mei Teo; Howard H F Tang; Danny Mok; Louise M Judd; Stephen C Watts; Kym Pham; Barbara J Holt; Merci Kusel; Michael Serralha; Niamh Troy; Yury A Bochkov; Kristine Grindle; Robert F Lemanske Jr; Sebastian L Johnston; James E Gern; Peter D Sly; Patrick G Holt; Kathryn E Holt; Michael Inouye

doi:10.1016/j.chom.2018.08.005

Airway Microbiota Dynamics Uncover a Critical Window for Interplay of Pathogenic Bacteria and Allergy in Childhood Respiratory Disease

Cell Host Microbe. 2018 Sep 12;24(3):341-352.e5. doi: 10.1016/j.chom.2018.08.005.

Authors

Shu Mei Teo¹, Howard H F Tang², Danny Mok³, Louise M Judd⁴, Stephen C Watts⁴, Kym Pham⁵, Barbara J Holt³, Merci Kusel³, Michael Serralha³, Niamh Troy³, Yury A Bochkov⁶, Kristine Grindle⁶, Robert F Lemanske Jr⁶, Sebastian L Johnston⁷, James E Gern⁶, Peter D Sly⁸, Patrick G Holt⁹, Kathryn E Holt¹⁰, Michael Inouye¹¹

Affiliations

¹ Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3010, Australia.
² Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; School of BioSciences, The University of Melbourne, Parkville, VIC 3010, Australia.
³ Telethon Kids Institute, The University of Western Australia, West Perth, WA, Australia.
⁴ Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3010, Australia.
⁵ Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia.
⁶ University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
⁷ Airway Disease Infection Section and MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, National Heart and Lung Institute, Imperial College London, Norfolk Place, London W2 1PG, UK.
⁸ Child Health Research Centre, The University of Queensland, Brisbane 4101, Australia.
⁹ Telethon Kids Institute, The University of Western Australia, West Perth, WA, Australia; Child Health Research Centre, The University of Queensland, Brisbane 4101, Australia.
¹⁰ Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3010, Australia; Telethon Kids Institute, The University of Western Australia, West Perth, WA, Australia; The London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK. Electronic address: [email protected].
¹¹ Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; School of BioSciences, The University of Melbourne, Parkville, VIC 3010, Australia; Telethon Kids Institute, The University of Western Australia, West Perth, WA, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia; The Alan Turing Institute, London, UK. Electronic address: [email protected].

Abstract

Repeated cycles of infection-associated lower airway inflammation drive the pathogenesis of persistent wheezing disease in children. In this study, the occurrence of acute respiratory tract illnesses (ARIs) and the nasopharyngeal microbiome (NPM) were characterized in 244 infants through their first five years of life. Through this analysis, we demonstrate that >80% of infectious events involve viral pathogens, but are accompanied by a shift in the NPM toward dominance by a small range of pathogenic bacterial genera. Unexpectedly, this change frequently precedes the detection of viral pathogens and acute symptoms. Colonization of illness-associated bacteria coupled with early allergic sensitization is associated with persistent wheeze in school-aged children, which is the hallmark of the asthma phenotype. In contrast, these bacterial genera are associated with "transient wheeze" that resolves after age 3 years in non-sensitized children. Thus, to complement early allergic sensitization, monitoring NPM composition may enable early detection and intervention in high-risk children.

Keywords: airway microbiota; allergic sensitization; asthma; lower respiratory infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute Disease
Asthma / diagnosis
Asthma / prevention & control
Child, Preschool
Cohort Studies
Disease Susceptibility / blood
Disease Susceptibility / microbiology
Disease Susceptibility / virology
Female
Humans
Hypersensitivity / diagnosis
Hypersensitivity / prevention & control
Immunoglobulin E / blood*
Infant
Longitudinal Studies
Male
Microbiota / genetics*
Nasopharynx / microbiology*
Nasopharynx / virology*
Prospective Studies
Respiratory Sounds
Respiratory Tract Infections / blood
Respiratory Tract Infections / microbiology*
Respiratory Tract Infections / virology*
Risk Factors

Substances

Immunoglobulin E

Abstract

Publication types

MeSH terms

Substances

Grants and funding