Bronchopulmonary dysplasia (BPD) is the most frequent respiratory complication in extremely preterm infants. It leads to significant mortality and long-term morbidity. The pathophysiology of BPD is multifactorial, involving inflammation and oxidative stress due to neonatal exposures such as mechanical ventilation and infections. Previous studies have highlighted the role of respiratory bacterial microbiota in BPD development, with causal effects having been demonstrated in murine models. Moreover, the gut-lung axis is implicated in BPD, with alterations to the gut bacteriome and mycobiome observed in preterm infants in the first weeks of life who later develop BPD. Despite its critical role in shaping immunity and microbial ecology, the virome has been largely understudied in preterm infants. Our recent observations have revealed the existence of a detectable respiratory virome at birth in most very preterm infants, and certain virome and bacteriome profiles have been found to be associated with different risks of developing BPD. Hypothesis: The early acquisition and dynamics of the respiratory and gut virome in the first weeks of life influence microbiome structure and pulmonary immune development, contributing to BPD pathogenesis. These dynamics may define distinct endotypes of BPD with implications for prognosis and therapy. Objectives: * Primary: Characterize the evolution of the respiratory and gut virome during the first 3 weeks of life in infants born \<30 weeks of gestation, comparing those who develop BPD to those who do not. * Secondary: * Define different BPD endotypes and assess their association with demographic and clinical characteristics * Characterise the structure of the microbiome within each endotype. * Compare the evolution of the virome, bacteriome and mycobiome within and between anatomical sites. Study Design: A monocentric, prospective observational cohort of 40 preterm infants (\<30 weeks GA) requiring respiratory support at birth. Infants are classified at 36 weeks' postmenstrual age (PMA) into BPD and non-BPD groups based on oxygen dependency. Sample Collection: * Oropharyngeal aspirates: Collected at days 0, 7, 14, and 21. * Stool samples: Collected at days 7, 14, and 21. Methods: * Virome analysis: Viral metagenomics * Metatranscriptomics: Assess transcriptionally active bacteria/fungi and host gene expression. * Data integration: Multi-omics factor analysis and unsupervised clustering to identify BPD endotypes; ecological network analysis to evaluate microbiome structure and interactions. Outcomes: * Primary: Qualitative and quantitative assessment of virome composition and diversity, including dynamics and persistence across timepoints. * Secondary: Definition of microbiome-based endotypes; interaction networks between viruses, bacteria, and fungi; and longitudinal comparisons of microbial diversity and composition across anatomical sites.
Bronchopulmonary dysplasia (BPD) is the most frequent respiratory complication in extremely preterm infants. It leads to significant mortality and long-term morbidity. The pathophysiology of BPD is multifactorial, involving inflammation and oxidative stress due to neonatal exposures such as mechanical ventilation and infections. Previous studies have highlighted the role of respiratory bacterial microbiota in BPD development, with causal effects having been demonstrated in murine models. Moreover, the gut-lung axis is implicated in BPD, with alterations to the gut bacteriome and mycobiome observed in preterm infants in the first weeks of life who later develop BPD. Despite its critical role in shaping immunity and microbial ecology, the virome has been largely understudied in preterm infants. Our recent observations have revealed the existence of a detectable respiratory virome at birth in most very preterm infants, and certain virome and bacteriome profiles have been found to be associated with different risks of developing BPD. Hypothesis: The early acquisition and dynamics of the respiratory and gut virome in the first weeks of life influence microbiome structure and pulmonary immune development, contributing to BPD pathogenesis. These dynamics may define distinct endotypes of BPD with implications for prognosis and therapy. Objectives: * Primary: Characterize the evolution of the respiratory and gut virome during the first 3 weeks of life in infants born \<30 weeks of gestation, comparing those who develop BPD to those who do not. * Secondary: * Define different BPD endotypes and assess their association with demographic and clinical characteristics * Characterise the structure of the microbiome within each endotype. * Compare the evolution of the virome, bacteriome and mycobiome within and between anatomical sites. Study Design: A monocentric, prospective observational cohort of 40 preterm infants (\<30 weeks GA) requiring respiratory support at birth. Infants are classified at 36 weeks' postmenstrual age (PMA) into BPD and non-BPD groups based on oxygen dependency. Sample Collection: * Oropharyngeal aspirates: Collected at days 0, 7, 14, and 21. * Stool samples: Collected at days 7, 14, and 21. Methods: * Virome analysis: Viral metagenomics * Metatranscriptomics: Assess transcriptionally active bacteria/fungi and host gene expression. * Data integration: Multi-omics factor analysis and unsupervised clustering to identify BPD endotypes; ecological network analysis to evaluate microbiome structure and interactions. Outcomes: * Primary: Qualitative and quantitative assessment of virome composition and diversity, including dynamics and persistence across timepoints. * Secondary: Definition of microbiome-based endotypes; interaction networks between viruses, bacteria, and fungi; and longitudinal comparisons of microbial diversity and composition across anatomical sites.
Study Type
OBSERVATIONAL
Enrollment
40
Viral metagenomics and metatranscriptomics will be performed following standardised protocol (published https://doi.org/10.1186/s12879-018-3446-5 and https://doi.org/10.3389/fmicb.2025.1685035) on oropharyngeal aspirates collected at days 0, 7, 14, and 21 and on stool samples collected at days 7, 14, and 21.
Qualitative and quantitative variations in the composition and diversity of the oropharyngeal and digestive viromes in DBP and control patients.
Composition is defined as the relative and absolute abundance of viral species, including both prokaryotic (e.g. bacteriophages) and eukaryotic (e.g. Anelloviridae and Herpesviridae) viruses. Analysis of compositional dynamics is defined by variations in the abundance of each species between samples, as well as by the persistence time of each viral species for each patient. Diversity is defined by richness (the number of species present) and the Shannon index. Diversity analysis is performed on the entire virome and on eukaryotic viruses, temperate bacteriophages and virulent bacteriophages separately. DBP presence is defined as oxygen dependence at 36 weeks PMA.
Time frame: through study completion, an average of 1 year
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