Abstract
<title>Abstract</title> <p> Systemic sclerosis (SSc) is a complex autoimmune disorder that has been associated with gut microbial dysbiosis. In this study, we analyzed the characteristics of the gut microbiome composition and function in SSc patients and explored associations between microbial features and clinical phenotypes. Fecal samples from 42 individuals (30 SSc patients and 12 healthy controls, HC) were subjected to shotgun metagenomic sequencing. SSc patients were further stratified into subgroups with (SSc-G+, n = 17) and without (SSc-G-, n = 13) gastrointestinal involvement based on University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0) scores. While alpha diversity did not differ significantly among groups, beta diversity analysis revealed distinct microbial community structures between HC and both SSc subgroups. Additionally, SSc patients exhibited a higher abundance of oral-associated bacteria at the species level, including <italic>Streptococcus salivarius</italic> and <italic>Streptococcus parasanguinis</italic> . Conversely, butyrate-producing bacteria, including <italic>Roseburia inulinivorans</italic> and <italic>Faecalibacterium prausnitzii</italic> , were more abundant in the HC group. Functional analysis identified 90 differentially abundant MetaCyc pathways enriched in the SSc groups, involved in amino acid, vitamin, and sugar metabolism. Gut Metabolic Modules (GMMs) analysis further indicated increased predicted ethanol production and amino acid degradation in SSc patients. Exploratory clinical association analysis identified associations between 23 microbial features and clinical variables, including a correlation between <italic>Ligilactobacillus salivarius</italic> and Raynaud’s phenomenon. Our findings suggest distinct gut microbial dysbiosis in SSc patients, characterized by enrichment of oral-associated taxa and metabolic shifts that may be relevant to disease pathogenesis. Further studies with larger cohorts are needed to validate these observations and elucidate mechanistic links between gut microbiota and SSc. </p>