Untargeted Metabolomics Revealed Metabolomic Profile in Patients with Primary Systemic Sclerosis.

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by increased morbidity and mortality. The intestinal microbiome and serum metabolites had been implicated in SSc, but the connection between the gut microbiome and serum metabolites remains poorly understood. In this study, we aimed to investigate the relationship between the gut microbiome and serum metabolome in SSc patients. Untargeted metabolomics was employed to examine the metabolic profiles of SSc patients. The results revealed significant alterations in metabolic pathways, particularly beta-alanine metabolism and pyrimidine metabolism in SSc patients. Specifically, reductions in spermine and beta-alanine were observed within beta-alanine metabolism, while uridylic acid decreased in pyrimidine metabolism. Furthermore, fecal microbiome analysis showed an increased relative abundance of Firmicutes, Verrucomicrobia, and Proteobacteria in SSc patients, whereas the abundance of Bacteroidetes and Actinobacteria was reduced at the phylum level. KEGG pathway analysis, combined with transcriptomic analysis of peripheral blood from SSc patients, identified upregulation of Toll-like receptor signaling, TNF signaling, lipid and atherosclerosis pathways, IL-17 signaling, and AMPK signaling. In summary, we performed a comprehensive analysis of the metabolic profile, which may provide insights for understanding the mechanisms of SSc.