Early Respiratory Microbiota Composition Determines Bacterial Succession Patterns and Respiratory Health in Children

Biesbroek, Giske; Tsivtsivadze, Evgeni; Sanders, Elisabeth A. M.; Montijn, R.C.; Veenhoven, Reinier H.; Keijser, Bart J. F.; Bogaert, Debby

doi:10.1164/rccm.201407-1240oc

Cited by 486 publications

(597 citation statements)

References 43 publications

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“…Тем самым, описанный выше DysbiosisInflammation Cycle [3] может манифестиро-вать с первичного дисбиоза носоглотки [52,53], развившегося с участием материнского ми-кроокружения, способа родоразрешения, пато-логии перинатального периода, особенностей вскармливания на первом году жизни и факто-ров макроокружения (в том числе вирусной на-грузки на ребенка) [47].…”

Section: Fundamental and Clinical Medicineunclassified

Upper Respiratory Dysbiosis in Children

Шабалдина¹,

Шабалдин²

2017

FCM

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Section: Fundamental and Clinical Medicineunclassified

Upper Respiratory Dysbiosis in Children

Шабалдина¹,

Шабалдин²

2017

FCM

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“…Early life colonisation by specific bacteria may play an important role in respiratory health and disease, with some species associated with number and frequency of ARI and the subsequent development of asthma (5,18,19).…”

Section: Upper Respiratory Microbiotamentioning

confidence: 99%

“…Longitudinal studies profiling the nasopharyngeal microbiota from Australia and Europe suggest that as early as 6 weeks after birth, the nasopharynx is colonised by species of typically skindwelling bacteria, such as Staphylococcus or Corynebacterium (5,17,18). Over time these species are replaced with stable colonisation by Moraxella or Alloiococcus/Dolosigranulum, with transient acquisition of Streptococcus and Haemophilus (5,17,18).…”

Section: Upper Respiratory Microbiotamentioning

confidence: 99%

“…Over time these species are replaced with stable colonisation by Moraxella or Alloiococcus/Dolosigranulum, with transient acquisition of Streptococcus and Haemophilus (5,17,18). Stable profiles such as those dominated…”

Section: Upper Respiratory Microbiotamentioning

confidence: 99%

“…by Moraxella or Alloiococcus/Dolosigranulum have been associated with breastfeeding and fewer ARI episodes in some studies (18), although Moraxella has also been associated with ARI episodes in others (5). The species S. pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are common opportunistic pathogens in young children, carried asymptomatically as well as capable of respiratory disease (22)(23)(24).…”

Section: Upper Respiratory Microbiotamentioning

confidence: 99%

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Viral/bacterial respiratory tract co-infections in children

Brealey¹

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Respiratory syncytial virus (RSV) is the most significant cause of paediatric acute respiratory infection (ARI). RSV and other respiratory viruses are commonly co-detected with potentially pathogenic bacteria, such as Streptococcus pneumoniae, in the upper airways of young children.While these bacteria are known to be carried asymptomatically, they are also capable of opportunistic infections. Interactions between RSV and S. pneumoniae have been demonstrated in both clinical and molecular studies. However, the clinical significance of these interactions remains debated, and the effect of clinically relevant strain variation in both virus and bacteria on these interactions is also unknown. This work aimed to better understand the role of S. pneumoniae colonisation during RSV infections.To determine the effect of RSV and S. pneumoniae co-detection on disease severity during ARI, molecular pathogen screening of nasopharyngeal samples was conducted in a cohort of young children under the age of two years presenting with ARI at the emergency department of the Royal Brisbane Children's Hospital, Australia. S. pneumoniae was co-detected in approximately 52% of RSV infections, and co-detection was associated with increased disease severity, suggesting that S. pneumoniae plays a pathogenic role in severe paediatric RSV infections.Having established a clinical role for S. pneumoniae during RSV infection, the dynamics of pneumococcal colonisation of the nasal cavity was investigated in the four weeks prior and subsequent to an RSV infection in a longitudinal birth cohort of Brisbane-based children.Approximately 33% of infants and young children with RSV infections were colonised by S. pneumoniae prior to the RSV detection, and strain characterisation of S. pneumoniae in the weeks immediately surrounding the viral infection suggested that any observed growth of S. pneumoniae during RSV infection arose from the pre-existing strain colonising the URT. In another 14% of RSV infections, S. pneumoniae was first detected during the virus infection, suggesting simultaneous acquisition of RSV and S. pneumoniae and possible co-transmission of the two pathogens.The results from the two paediatric cohorts suggested an interaction between RSV and S.pneumoniae that was advantageous to the bacteria. It was therefore hypothesised that the molecular mechanisms governing RSV and S. pneumoniae interactions might be pneumococcal strain-specific and stronger in strains frequently co-detected with RSV. Studies have shown that RSV can increase S. pneumoniae colonisation by enhancing pneumococcal adherence to airway epithelia, and virions iii can bind directly to the bacterium to form co-pathogen complexes. These interactions are in part mediated through the binding interactions between S. pneumoniae surface receptors and the RSV G surface glycoprotein. RSV G is highly variable, both antigenically and genetically, and is the main protein used to type RSV into subtypes A and B. The genetic variation of RSV G was characterised from nasophar...

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Prenatal and Infant Exposure to Acid-Suppressive Medications and Risk of Allergic Diseases in Children

et al. 2023

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ImportanceExisting observational data have indicated positive associations of acid-suppressive medication (ASM) use in prenatal and early life with allergic diseases in children; however, no study to date has accounted for confounding by indication or within-familial factors.ObjectiveTo evaluate the association of prenatal or infant exposure to ASMs with risk of allergic diseases in children.Design, Setting, and ParticipantsThis nationwide, cohort study included data from South Korea’s National Health Insurance Service mother-child–linked database from January 1, 2007, to December 31, 2020. Participants included mother-child pairs of neonates born from April 1, 2008, to December 31, 2019.ExposuresPrenatal and infant exposure to ASMs (histamine 2 receptor antagonists [H2RAs] and proton pump inhibitors [PPIs]).Main Outcomes and MeasuresComposite and individual outcomes of allergic diseases (asthma, allergic rhinitis, atopic dermatitis, and food allergy) in children (followed up to 13 years of age) were assessed. The ASM-exposed individuals were compared with unexposed individuals in propensity score (PS)–matched and sibling-matched analyses to control for various potential confounders and within-familial factors. Hazard ratios (HRs) with 95% CIs were estimated using Cox proportional hazards regression models.ResultsThe study included 4 149 257 mother-child pairs. Prenatal exposure analyses included 808 067 PS-matched pairs (763 755 received H2RAs, 36 529 received PPIs) among women with a mean (SD) age of 31.8 (4.2) years. The PS-matched HR was 1.01 (95% CI, 1.01-1.02) for allergic diseases overall (asthma: HR, 1.02 [95% CI, 1.01-1.03]; allergic rhinitis: HR, 1.02 [95% CI, 1.01-1.02]; atopic dermatitis: HR, 1.02 [95% CI, 1.01-1.02]; food allergy: HR, 1.03 [95% CI, 0.98-1.07]); in sibling-matched analyses, the HRs were similar to those of PS-matched analyses but were not significant (allergic diseases: HR, 1.01; 95% CI, 0.997-1.01). Infant exposure analyses included 84 263 PS-matched pairs (74 188 received H2RAs, 7496 received PPIs). The PS-matched HR was 1.06 (95% CI, 1.05-1.07) for allergic diseases overall (asthma: HR, 1.16 [95% CI, 1.14-1.18]; allergic rhinitis: HR, 1.02 [95% CI, 1.01-1.03]; atopic dermatitis: HR, 1.05 [95% CI, 1.02-1.08]; food allergy: HR, 1.28 [95% CI, 1.10-1.49]); asthma risk (HR, 1.13; 95% CI, 1.09-1.17) remained significantly higher among children exposed to ASMs during infancy in sibling-matched analyses. The findings were similar for H2RAs and PPIs analyzed separately and were robust across all sensitivity analyses.Conclusions and RelevanceThe findings of this cohort study suggest that there is no association between prenatal exposure to ASMs and allergic diseases in offspring. However, infant exposure to ASMs was associated with a higher risk of developing asthma, although the magnitude was more modest than previously reported. Clinicians should carefully weigh the benefits of prescribing ASMs to children, accompanied by subsequent close monitoring for any clinically relevant safety signals.

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Early Respiratory Microbiota Composition Determines Bacterial Succession Patterns and Respiratory Health in Children

Cited by 486 publications

References 43 publications

Upper Respiratory Dysbiosis in Children

Upper Respiratory Dysbiosis in Children

Viral/bacterial respiratory tract co-infections in children

Prenatal and Infant Exposure to Acid-Suppressive Medications and Risk of Allergic Diseases in Children

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