439 Evaluating the microbiome–immune crosstalk as a driver of inflammation in primary ciliary dyskinesia

Objectives/Goals: To examine gut microbiome–immune interactions that may contribute to respiratory dysfunction in Puerto Rican patients with primary ciliary dyskinesia (PCD), aiming to identify novel biomarkers that inform targeted interventions and address health disparities in rare diseases. Methods/Study Population: This cross-disciplinary pilot study integrates clinical, genomic, and microbiome data from patients with PCD carrying the Puerto Rican RSPH4A founder variant (c.921+3_6delAAGT; n = 8) and healthy controls (n = 8). Fecal samples will undergo 16S rRNA V4 sequencing and bioinformatic profiling using QIIME2, ANCOM, and PICRUSt2. Plasma cytokines (IL-6, IL-8, TNF-α, and IL-10), CRP, and ESR quantify systemic inflammation, while pulmonary tests (FEV₁ and FVC) will assess lung function. Correlation analyses will define microbial taxa linked to inflammatory and respiratory outcomes, elucidating the role of the gut–lung axis in disease progression. Results/Anticipated Results: We anticipate reduced microbial diversity and enrichment of pro-inflammatory taxa (e.g., Bacteroides and Prevotella) in PCD participants. Microbial shifts are expected to correlate with elevated inflammatory cytokines and decreased lung performance. These findings will highlight gut dysbiosis as a modifiable driver of inflammation, offering a foundation for future translational interventions such as diet or probiotic therapies. Discussion/Significance of Impact: This study advances precision medicine for rare lung diseases by elucidating gut–lung axis mechanisms in a genetically defined Puerto Rican PCD cohort, generating foundational data for future microbiome-targeted therapies and strengthening Puerto Rico’s translational research capacity.