Biochemistry and Pharmacology - Research Publications

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Type: Journal Article × Author: Holt, Kathryn × Author: Inouye, Michael × Author: Judd, Louise × End date: 2022 ×

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    Airway Microbiota Dynamics Uncover a Critical Window for Interplay of Pathogenic Bacteria and Allergy in Childhood Respiratory Disease
    Teo, SM ; Tang, HHF ; Mok, D ; Judd, LM ; Watts, SC ; Pham, K ; Holt, BJ ; Kusel, M ; Serralha, M ; Troy, N ; Bochkov, YA ; Grindle, K ; Lemanske, RF ; Johnston, SL ; Gern, JE ; Sly, PD ; Holt, PG ; Holt, KE ; Inouye, M (CELL PRESS, 2018-09-12)
    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.
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    Developmental patterns in the nasopharyngeal microbiome during infancy are associated with asthma risk
    Tang, HHF ; Lang, A ; Teo, SM ; Judd, LM ; Gangnon, R ; Evans, MD ; Lee, KE ; Vrtis, R ; Holt, PG ; Lemanske, RF ; Jackson, DJ ; Holt, KE ; Inouye, M ; Gern, JE (MOSBY-ELSEVIER, 2021-05)
    BACKGROUND: Studies indicate that the nasal microbiome may correlate strongly with the presence or future risk of childhood asthma. OBJECTIVES: In this study, we tested whether developmental trajectories of the nasopharyngeal microbiome in early life and the composition of the microbiome during illnesses were related to risk of childhood asthma. METHODS: Children participating in the Childhood Origins of Asthma study (N = 285) provided nasopharyngeal mucus samples in the first 2 years of life, during routine healthy study visits (at 2, 4, 6, 9, 12, 18, and 24 months of age), and during episodes of respiratory illnesses, all of which were analyzed for respiratory viruses and bacteria. We identified developmental trajectories of early-life microbiome composition, as well as predominant bacteria during respiratory illnesses, and we correlated these with presence of asthma at 6, 8, 11, 13, and 18 years of age. RESULTS: Of the 4 microbiome trajectories identified, a Staphylococcus-dominant microbiome in the first 6 months of life was associated with increased risk of recurrent wheezing by age 3 years and asthma that persisted throughout childhood. In addition, this trajectory was associated with the early onset of allergic sensitization. During wheezing illnesses, detection of rhinoviruses and predominance of Moraxella were associated with asthma that persisted throughout later childhood. CONCLUSION: In infancy, the developmental composition of the microbiome during healthy periods and the predominant microbes during acute wheezing illnesses are both associated with the subsequent risk of developing persistent childhood asthma.