Kofonow, J. | bioRxiv Science

bioRxiv2026

Altered Tonsillar Microbiome in Children with Down Syndrome and Obstructive Sleep Apnea

Background and ObjectivesChildren 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. MethodsTonsillar tissue from 22 DS and 18 NDS participants were analyzed by 16S rRNA sequencing. Alpha and beta diversity were assessed using Faiths phylogenetic diversity and UniFrac distances, respectively, and significantly different taxa were identified with ANCOM-BC and Mann-Whitney testing. ResultsAlthough 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. ConclusionsThese 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.

microbiology↗

bioRxiv2023

Microbiota-dependent indole production is required for the development of collagen-induced arthritis

Altered tryptophan catabolism has been identified in inflammatory diseases like rheumatoid arthritis (RA) and spondyloarthritis (SpA), but the causal mechanisms linking tryptophan metabolites to disease are unknown. Using the collagen-induced arthritis (CIA) model we identify alterations in tryptophan metabolism, and specifically indole, that correlate with disease. We demonstrate that both bacteria and dietary tryptophan are required for disease, and indole supplementation is sufficient to induce disease in their absence. When mice with CIA on a low-tryptophan diet were supplemented with indole, we observed significant increases in serum IL-6, TNF, and IL-1{beta}; splenic ROR{gamma}t+CD4+ T cells and ex vivo collagen-stimulated IL-17 production; and a pattern of anti-collagen antibody isotype switching and glycosylation that corresponded with increased complement fixation. IL-23 neutralization reduced disease severity in indole-induced CIA. Finally, exposure of human colon lymphocytes to indole increased expression of genes involved in IL-17 signaling and plasma cell activation. Altogether, we propose a mechanism by which intestinal dysbiosis during inflammatory arthritis results in altered tryptophan catabolism, leading to indole stimulation of arthritis development. Blockade of indole generation may present a novel therapeutic pathway for RA and SpA.

immunology↗