Age, chronic lung disease, and IgA levels influence the perturbation of respiratory microbial ecosystems in Common Variable Immunodeficiency

Background The respiratory tract microbiome is essential for human health and well-being and is determined by genetic, lifestyle, and environmental factors. Patients with Common Variable Immunodeficiency (CVID) suffer from respiratory and intestinal tract infections, leading to chronic diseases and increasing mortality. Alterations in CVID gut microbiota have been extensively analysed, while data on the respiratory microbiome ecosystem are limited. Methods The microbiome of oropharyngeal samples from 72 CVID adult patients and 26 age-matched controls were collected in a 12-month prospective study. Samples were analysed by metagenomic bacterial 16S ribosomal RNA sequencing and processed using the Quantitative Insights Into Microbial Ecology pipeline. Differentially abundant species have been identified and used to build a dysbiosis index. Microbiome alterations allowed the distinction between CVID and healthy status using a machine learning model trained on microbial abundance data. Results The oropharyngeal microbiome of CVID patients showed lower alpha- and beta-diversity, with a relatively increased abundance of the order Lactobacillales including the family Streptococcaceae. Undetectable serum IgA and COPD were associated with the higher abundance of the genera Haemophilus and Streptococcus, independently from recent antibiotic use. Patients with COPD featured a higher dysbiosis score. Conclusions Adult CVID patients showed an altered respiratory microbial ecosystem with enrichment with potentially pathogenic bacteria and decreased potentially protective species. Treatment aimed to replace mucosal IgA and possibly reduce upper respiratory infections by immunobiotics should gain attention.