Early-life host-microbial cross-talk in the lung

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Science Translational Medicine  19 Dec 2018:
Vol. 10, Issue 472, eaaw0527
DOI: 10.1126/scitranslmed.aaw0527


Early-life bacterial colonization patterns of the lower airways are an important determinant of the priming of the immune system.

When scientists started using culture-independent techniques to look for microbial communities in the lower airways, they were challenged by the preconception that the lungs were sterile. Even though the lung is in direct contact with the external world through the air that we breathe and by mucosal continuity with the mouth, the common dogma was that the lower airways did not contain bacteria. Host-microbiota interactions occurring in other mucosae had shown that resident microbes shape early-life immune responses. Pattaroni et al. now demonstrate that the lower airway is not an exception.

One of the most unusual features of this study is the use of lower airway (tracheal aspirates) samples obtained from 52 children with an age range of 1 day to 1 year old. To sample the “healthy” lungs of children and to avoid a difficult-to-justify invasive procedure, the authors enrolled children who underwent endotracheal intubation for elective surgery or respiratory support and excluded those with clinical evidence of infection, sepsis, or meconium aspiration. For all subjects, they performed microbiome analysis, and a small subgroup (n = 16) underwent parallel evaluation of local host transcriptomics.

The authors identified signs of microbial colonization as early as one day of life. In these children, there were three types of microbiota profiles in the lower airways: two of them were dominated by either Staphylococcus or Ureaplasma genera, whereas a third one was enriched with a diverse mixture of oral commensals, such as Streptococcus, Prevotella, Porphyromonas, and Veillonella. The first two patterns were preferentially found in the first few weeks, especially among preterm neonates, whereas microbiota enriched with oral commensals (a pattern commonly described in adults) became more prevalent over time. The composition of the lower airway microbiota was associated with gestational age and delivery mode: Ureaplasma (a common genital tract commensal)–dominated microbiota was associated with preterm vaginal delivery, and Staphylococcus-dominated microbiota was associated with preterm cesarean delivery. The authors hypothesized that the disappearance of Ureaplasma and Staphylococcus-dominated microbiota among preterm children beyond 30 weeks of gestational age might be related to the increasing amounts of surfactant in the lung, with may provide a different lipid-rich environment and support more diverse microbiota. Additionally, a prediction of virulence potential using a custom analytical pipeline identified that term delivery was associated with enrichment of immunoglobulin A1 protease function. The parallel evaluation of host transcriptomics in a subset of subjects showed distinct RNA expression patterns associated with distinct microbial communities. For example, there was an increase in RNA annotated to IgA pathways with greater gestational age. The concordance between the microbial immunoglobulin A1 protease signature and host IgA signature suggests a tight host-microbe interaction in the lower airways, which may influence immune maturation.

The cross-sectional design and correlative nature of this investigation are limitations of this manuscript, which would be difficult to overcome in human studies. However, the careful consideration of gestational age supports the idea that the constitution of the lower airway microbiota influences lower airway immune maturation. Future investigations should focus on understanding how these early events affect host susceptibility to inflammatory processes and infections.

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