Altered tonsillar microbiome in children with Down syndrome and obstructive sleep apnea

Abstract Background and Objectives Children with Down syndrome (DS) have a high prevalence of obstructive sleep apnea (OSA) due to anatomic, neuromuscular, immunological and metabolic factors, yet the contribution of the tonsillar microbiome to airway obstruction in this population remains unexplored. We hypothesized that DS-associated OSA would be associated with a distinct tonsillar microbiome compared to non-DS OSA. Methods Tonsillar tissue from 22 DS and 18 NDS participants were analyzed by 16S rRNA sequencing. Alpha and beta diversity were assessed using Faith’s phylogenetic diversity and UniFrac distances, respectively, and significantly different taxa were identified with ANCOM-BC and Mann–Whitney testing. Results Although overall microbial richness and community structure were similar between groups, overweight DS participants demonstrated increased phylogenetic diversity compared to normal-weight DS peers. Taxonomic profiling of the entire patient cohort revealed that in DS tonsils there were selective alterations in key genera with selective depletion of Haemophilus and enrichment of Staphylococcus , Rothia , and Lactobacillales . Haemophilus abundance correlated positively with tonsil weight in both cohorts. Conclusions These findings suggest that while global diversity is preserved, specific microbial shifts distinguish the DS tonsillar niche, potentially reflecting altered immune and metabolic environments associated with trisomy 21. Understanding these microbial differences may reveal mechanisms underlying the higher incidence and persistence of OSA in DS and inform targeted therapeutic strategies.