The following is a summary of “Human genetic associations of the airway microbiome in chronic obstructive pulmonary disease,” published in the April 2024 issue of Pulmonology by Gao et al.
Understanding the intricate interplay between human genetics and the airway microbiome remains a significant area of inquiry, particularly in chronic obstructive pulmonary disease (COPD). Leveraging deep metagenomic sequencing of sputum samples from 99 patients with COPD and 36 healthy individuals, researchers investigated the co-profiling of microbiome and host genetics, revealing over 5 million single nucleotide polymorphisms (SNPs).
Notably, host genetic variation emerged as a primary determinant influencing the airway microbiome, geography, and disease status, with the top 5 principal components accounting for 12.11% of microbiome variability. Among patients with COPD, 113 SNPs linked to candidate genes associated with COPD exhibited significant correlations with 29 microbial species and 48 functional modules (P < 1 × 10-5), with Streptococcus salivarius displaying the most robust association with SNP rs6917641 in TBC1D32 (P = 9.54 × 10-5). Integration of concurrent host transcriptomic data further unveiled correlations between the expression of host genes and genetically-linked microbiome features, highlighting potential interactions involving NUDT1, MAD1L1, and Veillonella parvula, TTLL9, and Stenotrophomonas maltophilia, as well as LTA4H and Haemophilus influenzae. Additionally, Mendelian randomization analyses uncovered a potential causal relationship between PARK7 expression and microbial type III secretion system, alongside a genetically-mediated association between COPD and elevated relative abundance of airway Streptococcus intermedius.
These findings underscore the significant role of host genetics in shaping the airway microbiome landscape and offer novel insights into genetic-based host-microbiome interactions in COPD, thereby paving the way for further exploration into the complex mechanisms underlying disease pathogenesis and potential therapeutic interventions.
Source: respiratory-research.biomedcentral.com/articles/10.1186/s12931-024-02805-2
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