Both transient tachypnea of the newborn and neonatal respiratory distress syndrome have been associated with changes in gene expression of aquaporine-5 (AQP5) and the β subunit of the epithelial sodium channel (β-ENaC) in the respiratory epithelium. Gastric aspirate (GA) obtained immediately after birth could represent a new source for gene expression analysis for these respiratory diseases. The aims of this study were to determine the feasibility of estimating AQP5 and β-ENaC gene expression in exfoliated respiratory epithelial cells from the GA of term neonates, and to compare the values with those found in scraped nasal epithelial cells, previously validated as a surrogate for distal lung epithelium in terms of ionic channel activity. The study had a cross-sectional, proof-of-concept design. Immediately after birth, we obtained GA and nasal mucous membrane scrapings from term newborns, in which total RNA and RT-qPCR assays for AQP5 and β-ENaC genes were performed. AQP5 gene expression was greater in GA than in nasal scrapings, and β-ENaC gene expression was at least as great in GA as that obtained in nasal scrapings. Amplification of samples from the two sites was comparable. AQP5 gene expression was greater in babies delivered by cesarean section; β-ENaC gene expression was greater in babies delivered vaginally, but only in the nasal samples. Quantitation of the expression of AQP5 and of β-ENaC genes in GA, obtained shortly after birth from term newborns is feasible. If confirmed in preterm neonates, this approach could aid in the differential diagnosis of neonatal respiratory diseases.

The link between gut and lung starts as early as during organogenesis. Even though they are anatomically distinct, essential bidirectional crosstalk via complex mechanisms supports GLA. Emerging studies have demonstrated the association of gut and lung diseases via multifaceted mechanisms. Advancements in omics and metagenomics technologies revealed a potential link between gut and lung microbiota, adding further complexity to GLA. Despite substantial studies on GLA in various disease models, mechanisms beyond microbial dysbiosis regulating the interplay between gut and lung tissues during disease conditions are not thoroughly reviewed. This review outlines disease specific GLA mechanisms, emphasizing research gaps with a focus on gut-to-lung direction based on current GLA literature. Moreover, the review discusses potential gut microbiota and their products like metabolites, immune modulators, and non-bacterial contributions as a basis for developing treatment strategies for lung diseases. Advanced experimental methods, modern diagnostic tools, and technological advancements are also highlighted as crucial areas for improvement in developing novel therapeutic approaches for GLA-related diseases. In conclusion, this review underscores the importance of exploring additional mechanisms within the GLA to gain a deeper understanding that could aid in preventing and treating a wide spectrum of lung diseases.