Yueming Cai

Objectives Systemic lupus erythematosus (SLE) is a complex autoimmune disease with unclear pathogenesis. Emerging evidence indicates that the gut microbiome may play a critical role in immune regulation. This study aimed to investigate gut microbiome and metabolome alterations in SLE patients, with a focus on the pro-inflammatory bacterium Clostridium scindens (C. scindens), and explore its potential contribution to disease pathogenesis. Method We performed metagenomic sequencing to analyze gut microbial composition in SLE patients and healthy controls, alongside untargeted metabolomic profiling of peripheral blood to assess systemic metabolic changes. We examined species diversity, taxonomic differences at both phylum and species levels, and metabolic alterations. Statistical analyses identified significant associations and potential diagnostic markers. Results SLE patients did not show a consistent reduction in species diversity, but exhibited significant microbial compositional differences compared to healthy controls. These patterns suggest potential diagnostic utility. Metabolomic analysis revealed systemic metabolic disturbances linked to gut dysbiosis. Ruminococcus gnavus was associated with altered amino acid, lactose, and sphingolipid metabolism, potentially affecting host immunity. Notably, C. scindens appeared to contribute to immune dysregulation via bile acid metabolism. Conclusions This study reveals distinct microbial and metabolic profiles in SLE, identifying C. scindens as a potential driver of immune imbalance. The findings suggest that targeting the gut microbiome could offer novel strategies for diagnosis and therapeutic intervention in SLE. Key Points • Gut microbial composition is significantly altered in SLE patients compared to healthy controls. • Metabolomic profiling reveals systemic disturbances linked to gut dysbiosis. • Clostridium scindens is associated with bile acid metabolism and immune dysregulation in SLE. • The gut microbiome may serve as a potential target for diagnosis and treatment in SLE.