Association of rhinovirus species with nasopharyngeal metabolome in bronchiolitis infants: A multicenter study

Fujiogi, Michimasa; Camargo, Carlos A.; Raita, Yoshihiko; Bochkov, Yury A.; Gern, James E.; Mansbach, Jonathan M.; Piedra, Pedro A.; Hasegawa, Kohei

doi:10.1111/all.14326

Cited by 15 publications

(13 citation statements)

References 11 publications

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“…In prior analyses without RV species–level resolution, nasopharyngeal 11 and circulating 12 metabolomic profiles differed between RSV and RV infection. Additionally, our group previously reported between‐virus differences in the nasopharyngeal metabolome 23 . For example, in the RSV vs RV‐A comparison, the discriminatory nasopharyngeal metabolites consisted mainly of nucleic and amino acids (such as guanine and cysteine‐glutathione disulfide).…”

Section: Discussionmentioning

confidence: 97%

Respiratory viruses are associated with serum metabolome among infants hospitalized for bronchiolitis: A multicenter study

Fujiogi

Camargo

Raita

et al. 2020

Pediatric Allergy Immunology

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Background: Bronchiolitis is the leading cause of infant hospitalizations in the United States. Growing evidence supports the heterogeneity of bronchiolitis. However, little is known about the interrelationships between major respiratory viruses (and their species), host systemic metabolism, and disease pathobiology. Methods: In an ongoing multicenter prospective cohort study, we profiled the serum metabolome in 113 infants (63 RSV-only, 21 RV-A, and 29 RV-C) hospitalized with bronchiolitis. We identified serum metabolites that are most discriminatory in the RSV-RV-A and RSV-RV-C comparisons using sparse partial least squares discriminant analysis. We then investigated the association between discriminatory metabolites with acute and chronic outcomes. Results: In 113 infants with bronchiolitis, we measured 639 metabolites. Serum metabolomic profiles differed in both comparisons (P permutation < 0.05). In the RSV-RV-A comparison, we identified 30 discriminatory metabolites, predominantly in lipid metabolism pathways (eg, sphingolipids and carnitines). In multivariable models, these metabolites were significantly associated with the risk of clinical outcomes (eg, tricosanoyl sphingomyelin, OR for recurrent wheezing at age of 3 years = 1.50; 95% CI: 1.05-2.15). In the RSV-RV-C comparison, the discriminatory metabolites were also primarily involved in lipid metabolism (eg, glycerophosphocholines [GPCs], 12,13-diHome). These metabolites were also significantly associated with the risk of outcomes (eg, 1-stearoyl-2-linoleoyl-GPC, OR for positive pressure ventilation use during hospitalization = 0.47; 95% CI: 0.28-0.78). Conclusion: Respiratory viruses and their species had distinct serum metabolomic signatures that are associated with differential risks of acute and chronic morbidities of bronchiolitis. Our findings advance research into the complex interrelations between viruses, host systemic response, and bronchiolitis pathobiology.

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Section: Discussionmentioning

confidence: 97%

Respiratory viruses are associated with serum metabolome among infants hospitalized for bronchiolitis: A multicenter study

Fujiogi

Camargo

Raita

et al. 2020

Pediatric Allergy Immunology

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“…Moreover, research has also suggested the role of metabolome—which represents the downstream functional products of the microbiome, child’s genetic make-up, and immune response—in the pathogenesis of bronchiolitis and asthma 2 . For example, a recent study of airway metabolome has shown differences in pro- and anti-inflammatory mediators (e.g., spermidine) in infants with bronchiolitis 12 . These studies—while limited to single-level data (e.g., clinical, virus, microbiome, cytokines/chemokines, metabolome)—have discovered potential mechanisms that underlie the bronchiolitis–asthma link.…”

Section: Discussionmentioning

confidence: 99%

“…While bronchiolitis has been considered a single disease with similar mechanisms 2 , emerging evidence suggests heterogeneity in clinical presentations 4 and chronic morbidities (e.g., subsequent risk of recurrent wheeze and asthma) 5 , 6 . Growing evidence also suggests distinct upper airway microbiome 7 , 8 , transcriptome 9 , cytokine 10 , 11 , and metabolome 12 profiles among infants with bronchiolitis. However, these findings have been solely derived from single-level (e.g., clinical or microbiome) data.…”

Section: Introductionmentioning

confidence: 99%

Integrated omics endotyping of infants with respiratory syncytial virus bronchiolitis and risk of childhood asthma

et al. 2021

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Respiratory syncytial virus (RSV) bronchiolitis is not only the leading cause of hospitalization in U.S. infants, but also a major risk factor for asthma development. While emerging evidence suggests clinical heterogeneity within RSV bronchiolitis, little is known about its biologically-distinct endotypes. Here, we integrated clinical, virus, airway microbiome (species-level), transcriptome, and metabolome data of 221 infants hospitalized with RSV bronchiolitis in a multicentre prospective cohort study. We identified four biologically- and clinically-meaningful endotypes: A) clinicalclassicmicrobiomeM. nonliquefaciensinflammationIFN-intermediate, B) clinicalatopicmicrobiomeS. pneumoniae/M. catarrhalisinflammationIFN-high, C) clinicalseveremicrobiomemixedinflammationIFN-low, and D) clinicalnon-atopicmicrobiomeM.catarrhalisinflammationIL-6. Particularly, compared with endotype A infants, endotype B infants—who are characterized by a high proportion of IgE sensitization and rhinovirus coinfection, S. pneumoniae/M. catarrhalis codominance, and high IFN-α and -γ response—had a significantly higher risk for developing asthma (9% vs. 38%; OR, 6.00: 95%CI, 2.08–21.9; P = 0.002). Our findings provide an evidence base for the early identification of high-risk children during a critical period of airway development.

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“…Investigators collected nasopharyngeal airway samples within 24 hours of hospitalization using a standardized protocol ( 9 ). These samples underwent A) real-time PCR to test for respiratory viruses ( 2 ), B) ultra-performance liquid chromatography–tandem mass spectrometry to profile the metabolome ( 10 ), and C) 16S rRNA gene sequencing to profile the microbiota ( 11 ).…”

Section: Methodsmentioning

confidence: 99%

Association of endemic coronaviruses with nasopharyngeal metabolome and microbiota among infants with severe bronchiolitis: a prospective multicenter study

et al. 2020

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Association of rhinovirus species with nasopharyngeal metabolome in bronchiolitis infants: A multicenter study

Abstract: Ungar B , et al. Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis .

Cited by 15 publications

References 11 publications

Respiratory viruses are associated with serum metabolome among infants hospitalized for bronchiolitis: A multicenter study

Respiratory viruses are associated with serum metabolome among infants hospitalized for bronchiolitis: A multicenter study

Integrated omics endotyping of infants with respiratory syncytial virus bronchiolitis and risk of childhood asthma

Association of endemic coronaviruses with nasopharyngeal metabolome and microbiota among infants with severe bronchiolitis: a prospective multicenter study

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