Nasopharyngeal airway dual-transcriptome of infants with severe bronchiolitis and risk of childhood asthma: A multicenter prospective study - 04/10/22
, Carlos A. Camargo, MD, DrPH a, Yoshihiko Raita, MD, MPH, MMSc a, Robert J. Freishtat, MD, MPH b, c, d, Michimasa Fujiogi, MD a, Andrea Hahn, MD, MS b, d, e, Jonathan M. Mansbach, MD, MPH f, Jonathan M. Spergel, MD, PhD g, Marcos Pérez-Losada, PhD h, i, Kohei Hasegawa, MD, MPH, MS aAbstract |
Background |
Severe bronchiolitis (ie, bronchiolitis requiring hospitalization) during infancy is a major risk factor for childhood asthma. However, the exact mechanism linking these common conditions remains unclear.
Objectives |
This study sought to examine the integrated role of airway microbiome (both taxonomy and function) and host response in asthma development in this high-risk population.
Methods |
This multicenter prospective cohort study of 244 infants with severe bronchiolitis (median age, 3 months) examined the infants’ nasopharyngeal metatranscriptomes (microbiomes) and transcriptomes (hosts), as well as metabolomes at hospitalization. The longitudinal relationships investigated include (1) major bacterial species (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis), (2) microbial function, and (3) host response with risks of developing asthma by age 6 years.
Results |
First, the abundance of S pneumoniae was associated with greater risks of asthma (P = .01), particularly in infants with nonrhinovirus infection (Pinteraction = .04). Second, of 328 microbial functional pathways that are differentially enriched by asthma development, the top pathways (eg, fatty acid and glycolysis pathways; false discovery rate [FDR] < 1 × 10−12) were driven by these 3 major species (eg, positive association of S pneumoniae with glycolysis; FDR < 0.001). These microbial functional pathways were validated with the parallel metabolome data. Third, 104 transcriptome pathways were differentially enriched (FDR < .05)—for example, downregulated interferon-α and -γ and upregulated T-cell activation pathways. S pneumoniae was associated with most differentially expressed transcripts (eg, DAGLB; FDR < 0.05).
Conclusions |
By applying metatranscriptomic, transcriptomic, and metabolomic approaches to a multicenter cohort of infants with bronchiolitis, this study found an interplay between major bacterial species, their function, and host response in the airway, and their longitudinal relationship with asthma development.
El texto completo de este artículo está disponible en PDF.Graphical abstract |
Key words : Bronchiolitis, asthma, dual-transcriptome, microbiome, transcriptome, metabolome, fatty acids, glycolysis
Abbreviations used : FDR, GO, MARC-35, rRNA, RNA-seq
Esquema
| Supported by grants from the National Institutes of Health (NIH) (K01 AI-153558, U01 AI-087881, R01 AI-114552, R01 AI-127507, R01 AI-134940, R01 AI-137091, R01 AI-148338, and UG3/UH3 OD-023253). M.P.-L. was partially supported by the Margaret Q. Landenberger Research Foundation, the NIH National Center for Advancing Translational Sciences (Award Number UL1TR001876), and the Fundação para a Ciência e a Tegnologia (T495756868-00032862). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding organizations were not involved in the collection, management, or analysis of the data; preparation or approval of the manuscript; or decision to submit the manuscript for publication. |
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| Disclosure of potential conflict of interest: Z. Zhu reports grants from NIH during the conduct of the study. C. A. Camargo reports grants from NIH during the conduct of the study. A. Hahn reports personal fees from Johnson and Johnson, outside the submitted work. J. M. Spergel reports grants and personal fees from Regeneron, grants and personal fees from Novartis, grants and personal fees from Sanofi, grants from Food Allergy Research Education, personal fees from Takeda, grants and personal fees from DBV Technologies, personal fees from Takeda, personal fees from Leo Pharmaceutical, personal fees from Readysetfood, personal fees from Syneos, outside the submitted work. K. Hasegawa reports grants from NIH during the conduct of the study; grants from Novartis, outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 150 - N° 4
P. 806-816 - octobre 2022 Regresar al número
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