The development of the respiratory microbiota in infants and children

Abstract

Background Pre-school wheeze is a common condition which causes considerable morbidity and burden to the child, their family and healthcare. The developing upper respiratory tract microbiota has been identified as a factor associated with respiratory health. The longitudinal development of the oropharyngeal (OP) microbiota in infants has not been described in detail. The aim of this thesis is to describe this development and a secondary aim is to examine its relation to preschool wheeze. Methods A cohort of healthy infants was established and followed from birth to 2 years of age. OP swabs and contemporaneous metadata were collected during home visits at 6 weeks, 6, 9, 12, 18 and 24 months. General practitioner notes were reviewed at 2 years for diagnosis of wheeze. The microbiota was determined using sequencing of the V3 to V5 region of the 16S rRNA gene. Respiratory viruses were detected using multiplex PCR. Results The OP microbiota increased in complexity over the first 2 years of life with a change in composition, density and diversity. Much of the change occurred within the first 9 months of life, when there was also increasing rates of respiratory virus infection. The OP microbiota was highly individual but was affected by clinical factors such as feeding choice. The early (6 weeks) microbiota was not associated with doctor-diagnosed wheeze in terms of diversity or composition. However, there was a longitudinal differential abundance (reduction in a Granulicatella Operational Taxonomic Unit (OTU) and an increase in a Neisseria OTU) in those diagnosed with wheeze compared to those who did not wheeze. Conclusions There was a temporal development of the OP microbiota and respiratory virus infection. Whilst there was no association with the early microbiota and doctor-diagnosed wheeze, there was an association with the longitudinal abundance of particular OTUs.