The composition of the upper respiratory tract (URT) microbiota is shaped by both anatomical niches and host immune defenses. Older adults (>65 years) are at greatest risk of acquiring severe URT infections. However, very little is known about whether age-related changes in the composition of the URT microbiota and host innate immunity contribute to this susceptibility to respiratory infection. We aimed to characterize age-related changes to the composition of the URT microbiota and investigate the modulation of host immune gene expression by microbiota community composition.
The mid-turbinate microbiotas of 270 adults between 20 and 100 years old were interrogated by 16S rRNA sequencing of nasal swabs. We identified dominant microbial subcommunities by latent Dirichlet allocation topic modeling. Dominant microbes, age, and nasal epithelium gene expression were correlated by mixed-effect models. Gene clusters examined include core macrophage markers, inflammatory macrophage genes, chemotaxis and migration genes, and neutrophil-associated genes.
Topic alignment identified 10 subcommunities in the URT microbiome dominated by the following species: Staphylococcus aureus, Staphylococcus caprae, Corynebacterium accolens 1, C. accolens 2, C. accolens 3, Corynebacterium propinquum, Moraxella catarrhalis, Moraxella catarrhalis, Corynebacterium tuberculostearicum, and Peptoniphilus grossensis. Subcommunities dominated by S. aureus and C. accolens had decreasing relative abundance with increasing age, though this was not statistically significant. The C. accolens 2-dominated subcommunity was more likely to be dominant and had higher relative abundance with increasing age. The nasal epithelium became more secretory and structurally robust with age, with a reduced expression of cellular plasticity and immune regulation genes. Inflammatory cytokine gene (IL1B, IL16, OSM, and SRGN) expression was significantly upregulated in microbial communities dominated by S. aureus, C. accolens 2, C. accolens 3, and C. propinquum. S. aureus- and C. propinquum-dominated communities also demonstrated significant upregulation of macrophage- and neutrophil-associated genes. In contrast, significant downregulation of macrophage- and neutrophil-associated genes was seen in S. caprae-dominated communities. We conclude that increasing age is associated with compositional changes in the adult URT microbiota, which further alter host innate immunity. Understanding age-related changes to the URT microbiota and immune defenses is essential to reduce susceptibility to respiratory infections.
