Compositional and Functional Profiling of the Gut Microbiome in Sarcoidosis

Abstract

BackgroundSarcoidosis is a chronic inflammatory disease characterized by systematic granuloma formation, predominantly in the lungs. One leading hypothesis posits that prolonged exposure to microbial antigens may trigger chronic and dysregulated inflammation. Prior studies have examined the lung microbiota of sarcoidosis patients, but the role of the gut microbiota along the gut-immune axis remains largely unexplored. We elucidate the community composition and function of the gut microbiome in sarcoidosis. MethodsSubjects diagnosed with sarcoidosis (n=37) were recruited and matched with healthy control subjects (n=37). Stool samples were collected from sarcoidosis patients for metagenomic sequencing, followed by taxonomic classification and functional annotation as KEGG Orthology (KO) pathways. Differential analysis between sarcoidosis and control cohorts was performed using both standard and compositional approaches. ResultsSarcoidosis microbiomes exhibited similar alpha diversity but significantly different beta diversity from control microbiomes (p1), including microbes previously detected in the lungs and granulomas of sarcoidosis. Functional profiling revealed 409 KO pathways that were significantly underrepresented in sarcoidosis compared to control (FDR 1. These include pathways in amino acid and energy metabolism as well as HIF-1 signaling. ConclusionsOur findings highlight the potential role of gut microbiome composition and function in inflammatory processes that are associated with granuloma formation in sarcoidosis and warrant further investigation into gut hyperoxia-driven dysbiosis.