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Bronchopulmonary dysplasia (BPD) is a common lung disease of premature infants. Hyperoxia exposure and microbial dysbiosis are contributors to BPD development. However, the mechanisms linking pulmonary microbial dysbiosis to worsening lung injury are unknown. Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that regulates oxidative stress responses and modulates hyperoxia-induced lung injury. We hypothesized that airway dysbiosis would attenuate Nrf2-dependent antioxidant function, resulting in a more severe phenotype of BPD. Here, we show that preterm infants with a Gammaproteobacteria-predominant dysbiosis have increased endotoxin in tracheal aspirates, and mice monocolonized with the representative Gammaproteobacteria show increased tissue damage compared with germ-free (GF) control mice. Furthermore, we show Nrf2-deficient mice have worse lung structure and function after exposure to hyperoxia when the airway microbiome is augmented with . To confirm the disease-initiating potential of airway dysbiosis, we developed a novel humanized mouse model by colonizing GF mice with tracheal aspirates from human infants with or without severe BPD, producing gnotobiotic mice with BPD-associated and non-BPD-associated lung microbiomes. After hyperoxia exposure, BPD-associated mice demonstrated a more severe BPD phenotype and increased expression of -regulated genes, compared with GF and non-BPD-associated mice. Furthermore, augmenting -mediated antioxidant activity by supporting colonization with species improved dysbiotic-augmented lung injury. Our results demonstrate that a lack of protective pulmonary microbiome signature attenuates an -mediated antioxidant response, which is augmented by a respiratory probiotic blend. We anticipate antioxidant pathways will be major targets of future microbiome-based therapeutics for respiratory disease.

Background MicroRNA (miR) are small conserved RNA that regulate gene expression post-transcription. Previous genome-wide analysis studies in preterm infants indicate that pathways of miR 219-5p are important in infants with Bronchopulmonary Dysplasia (BPD). Methods Here we report a prospective cohort study of extremely preterm neonates wherein infants diagnosed with severe BPD expressed increased airway miR-219-5p and decreased platelet derived growth factor receptor alpha (PDGFR-α), a target of mir-219-5p and a key regulator of alveolarization, compared to post-conception age-matched term infants. Results miR-219-5p was highly expressed in the pulmonary epithelial lining in lungs of infants with BPD by in situ hybridization of human infant lungs. In both in vitro and in vivo (mouse) models of BPD, miR-219-5p was increased on exposure to hyperoxia compared with the normoxia control, with a complementary decrease of PDGFR-α. To further confirm the target relationship between miR‐219 and PDGFR-α, pulmonary epithelial cells (MLE12) and lung primary fibroblasts were treated with a mimic of miR-219-5p and a locked nucleic acid (LNA) based inhibitor of miR-219-5p. In comparison with the control group, the level of miR‐219 increased significantly after miR‐219 mimic treatment, while the level of PDGFR-α declined markedly. LNA exposure increased PDGFR-α. Moreover, in BPD mouse model, over-expression of miR-219-5p inhibited alveolar development, indicated by larger alveolar spaces accompanied by reduced septation. Conclusions Taken together, our results demonstrate that increased miR-219-5p contributes to the pathogenesis of BPD by targeting and reducing PDGFR-α. The use of specific miRNA antagonists may be a therapeutic strategy for preventing the development of BPD.

Rationale Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity and significantly contributes to mortality and morbidity with few predictive biomarkers. Given that nitrites have been implicated in pathways associated with lung disease, we hypothesized that nitrite levels would be altered in the airways of premature infants diagnosed with BPD. Methods This was a prospective cohort study of extremely low birth infants (< 28 weeks’ gestation) at the University of Alabama at Birmingham. Nitrite levels from tracheal aspirates (TAs) were compared between intubated and ventilated infants with BPD and gestation matched full term (FT) controls. TA derived nitrite levels from day one after birth were also compared between preterm infants who did and did not develop BPD. Results Infants with BPD were found to have significantly elevated nitrite levels in their tracheal aspirates compared to gestation matched FT controls ( p  < 0.05). There was a trend for increased nitrite levels on postnatal day one in infants that developed BPD compared to infants that did not develop BPD ( p  = 0.05). Conclusions In conclusion, nitrite levels are significantly increased in airways of infants with BPD. Data from a larger cohort are needed to further support the utility of nitrite for BPD prediction. Trial registration Not applicable.

Dry eye affects millions of individuals. In experimental models, dry eye disease is associated with T helper cell 17-mediated inflammation of the ocular surface that may cause persistent damage to the corneal epithelium. However, the initiating and perpetuating factors associated with chronic inflammation of the ocular surface remain unclear. The ocular microbiota alters ocular surface inflammation and may influence dry eye disease development and progression. Here, we collected serial samples of tears on awakening from sleep, closed eye tears, during a randomized clinical trial of a non-pharmaceutical dry eye therapy and used 16S rRNA metabarcoding to characterize the microbiome. We show the closed dry eye microbiome is distinct from the healthy closed eye microbiome, and that the microbiome remains distinct despite daily saline eye wash upon awakening. The ocular microbiome was described only recently, and this report implicates a distinct microbiome in ocular disease development. Our findings suggest an interplay between microbial commensals and inflammation on the ocular surface. This information may inform future studies of the pathophysiological mechanisms of dry eye disease.

Coral reef ecosystems are under threat from a myriad of stressors, ranging from direct human stress (e.g. fishing) to global climate change (e.g. warming sea surface temperatures). Climate change will shift the fundamental habitats in which coral reefs reside. To better understand coral reef survival likelihood in future climate scenarios, these habitats are assessed in both present and future conditions. Classification of Pacific coral reefs by physico-chemical environment shows that there is in fact great complexity in coral reef habitat. Sea surface temperatures, aragonite saturation state, storm frequency, nutrient levels, and current speeds are all critical factors in determining physico-chemical habitat. A case study in the Hawaiian Islands indicates that these habitats are in part reflected in coral reef ecology, although it is difficult to tease apart the effects of ocean environment considering the myriad of human stressors to coral reefs. Future coral reef habitats are assessed for two climate change scenarios. Non-uniform habitat constriction is found worldwide. Reefs in the Caribbean Sea are particularly vulnerable to climate change. Reefs in the Indian Ocean are currently experiencing conditions quite similar to projected conditions worldwide, and are ideal candidate regions to select corals for re-wilding and translocation efforts. Finally, case study of regional oceanography in French Polynesia provides further insights into downscaling global projections to individual islands.