Cystic fibrosis (CF) lung disease begins early, and prophylactic antibiotics have been used to prevent Staphylococcus aureus infection. This study examined the lung microbiome in two countries with differing antibiotic practices and its relationship to lung function in young children with CF. A binational, longitudinal, observational study was performed to define the lower airway microbiome in infants with CF. 16S rRNA sequencing was performed using lavage fluid to characterize the lung microbiota in 45 infants with and without prophylactic antibiotic therapy at an average age of approximately 3 months and 14 months. The association between pulmonary function, bacterial community diversities, and taxa was assessed. Expected CF bacterial genera and non-traditional bacteria, such as Streptococcus, were identified as core taxa. Microbial community shifts were observed in infants who received antibiotic prophylaxis, with lower alpha diversity (ANOVA, P < 0.05) and a higher proportion of Streptococcus at the first visit. Beta diversity (FEV_0.5z; MiRKAT, P < 0.05) and Streptococcus were associated with FEV_0.5z (LASSO and linear regression, β < 0). Functional annotation suggested that alteration of lung microbiota may be linked to antimicrobial resistance. Lung microbial diversity in infants with CF varied between the two countries, particularly during early infancy. A shift in the lung microbiome toward a higher relative abundance of Streptococcus was associated with reduced pulmonary function.

Introduction: End-stage renal disease (ESRD) results in immune dysfunction that is characterized by both systemic inflammation and immune incompetence, leading to impaired responses to vaccination. Methods: To unravel the complex regulatory immune interplay in ESRD, we performed the network-based transcriptomic profiling of ESRD patients on maintenance hemodialysis (HD) and matched healthy controls (HCs) who received the two-dose regimen of the COVID-19 mRNA vaccine BNT162b2. Results: Co-expression networks based on blood transcription modules (BTMs) of genes differentially expressed between the HD and HC groups revealed co-expression patterns that were highly similar between the two groups but weaker in magnitude in the HD compared to HC subjects. These networks also showed weakened coregulation between BTMs within the dendritic cell (DC) family as well as with other BTM families involved with innate immunity. The gene regulatory networks of the most enriched BTMs, likewise, highlighted weakened targeting by transcription factors of key genes implicated in DC, natural killer (NK) cell, and T cell activation and function. The computational deconvolution of immune cell populations further bolstered these findings with discrepant proportions of conventional DC subtypes, NK T cells, and CD8+ T cells in HD subjects relative to HCs. Conclusion: Altogether, our results indicate that constitutive inflammation in ESRD compromises the activation of DCs and NK cells, and, ultimately, their mediation of downstream lymphocytes, leading to a delayed but intact immune response to mRNA vaccination.