The nasopharyngeal microbiome and LRTIs in infants

Acute lower respiratory tract infections (LRTIs) are a major source of early life morbidity and the principal infectious cause of infant mortality.¹ A growing body of research suggests that the microbiome of the upper respiratory tract substantially influences the incidence and severity of LRTIs. The nasopharyngeal mucosa is the first line of defence against airborne pathogens. In addition to the mechanisms of host innate immunity, the commensal microbiota suppresses the expansion of populations of opportunistic pathogens that are common in the nasopharynx—including Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus—through a combination of competitive exclusion, suppression of virulence through direct inter-species interaction, and regulation of local immunity.² Opportunistic pathogens thus have to overcome both host defences and the stabilising effects of the commensal microbiota to proliferate within the upper airways.

In The Lancet Respiratory Medicine, Wing Ho Man and colleagues³ investigate the links between the composition of the nasopharyngeal microbiome and the development of LRTIs in children. They first addressed an issue relating directly to clinical practice: whether assessments of nasopharyngeal microbiota might serve as a proxy for lower respiratory microbiota. To this end, they assessed nasopharyngeal swabs and endotracheal aspirates from a cohort of 29 infants hospitalised for LRTIs who required mechanical ventilation. The correspondence between the two sample types was notable, with near-complete agreement in viral detection and substantial concordance in bacterial community composition. By combining viral and bacterial biomarkers with host factors, the authors were able to correctly discriminate between LRTIs and health in 92% of instances on the basis of analysis of nasopharyngeal swabs, and 100% of instances on the basis of analysis of endotracheal aspirates. In view of the development of increasingly rapid analytic platforms, the ability to use such findings to guide clinical decisions through point-of-care diagnostics, including in the selection of antibiotics, becomes increasingly plausible. The high level of agreement between microbiota composition assessed with nasopharyngeal swabs and endotracheal aspirates is also encouraging with regards to the wider use of nasopharyngeal swabs to gain insight into lower airway microbiology. However, the extent to which the process of intubation itself contributes to this relationship remains unclear.

Man and colleagues also assessed how the composition of the nasopharyngeal microbiome affects LRTI risk in a prospectively enrolled case-control cohort of children hospitalised with LRTIs and a matched cohort of healthy children. They reported that the composition of the nasopharyngeal microbiota—but not bacterial biomass—differed significantly between children with LRTIs and healthy children. Domination of the microbiota by H influenzae and Haemophilus haemolyticus or by S pneumoniae was associated with LRTIs. These differences in microbiota composition persisted even when LRTI was stratified into distinct phenotypes (pneumonia, bronchiolitis, wheezing illness, or mixed), with Haemophilus, Neisseria, and oral taxa over-represented in children with LRTIs compared with healthy controls in each phenotype.

The predominance of Haemophilus spp in the nasopharynx has been associated with LRTIs in several previous studies, and seems to be more common when the resident microbiota have undergone a previous disruption.⁴ The effect of viral infection or other respiratory insults could result in changes to the composition of the commensal microbiota, including the displacement of keystone commensal taxa, which in turn degrade the microbiota's ability to suppress overgrowth by H influenzae or other common pathobionts and increase the likelihood of LRTI. Such disruption might also reduce the beneficial effect of the commensal microbiome on host response to respiratory viral infection.⁵ Such a schema could partly explain well described risk factors for LRTIs, including previous antibiotic therapy and respiratory viral infections, exposure to tobacco smoke, and a short duration of breastfeeding, all of which substantially affect the development and composition of nasopharyngeal microbiota.6, 7, 8

The identification of upper respiratory tract microbiome characteristics associated with LRTIs is an exciting development. The application of higher-resolution analytic techniques promises to further define these relationships. In particular, metagenomic approaches could extend models to include fungal and viral commensal populations in LRTIs, or the carriage of specific virulence traits or determinants of antibiotic resistance. Integration of analysis of common host genetic polymorphisms that affect susceptibility to viral and bacterial respiratory infections9, 10 might also help to improve prediction of the risk of LRTI.

Beyond identification of risk, measures that can reduce the incidence of LRTIs are essential. Clearly, efforts to reduce exposure to tobacco smoke, promote breastfeeding, and improve antibiotic stewardship are crucial. However, approaches that might restore immune tolerance and microbiota structure in at-risk infants should also be considered. A large-scale trial¹¹ in rural India showed a significant reduction in the frequency of LRTIs in infants given an oral synbiotic compared with those given placebo. Early-life intranasal administration of probiotics induces immune tolerance, reduces susceptibility to respiratory viral infection, and increases clearance of bacterial pathogens from the lower airways in murine models.12, 13 Such findings suggest the potential value of novel, microbiome-mediated, preventive strategies that aim to reduce host susceptibility, as an addition to pathogen-focused infection-control measures.

© 2019 Steve Gschmeissner/SPL