Abstract
Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disease driven by immune dysregulation. This study investigated the relationship between gut microbiota and lupus severity using the MRL/lpr lupus mouse model. Mice were grouped based on total immunoglobulin (Ig)G, IgG2a levels, and urine albumin-to-creatinine ratio (ACR), allowing for the comparison of gut microbiota profiles across different disease severities. Interestingly, severe lupus mice exhibited significant reductions in Ruminiclostridium cellulolyticum, Lactobacillus johnsonii, and Kineothrix alysoides, while Clostridium saudiense, Pseudoflavonifractor phocaeensis, and Intestinimonas butyriciproducens were enriched. These microbial shifts correlated with elevated IgG, IgG2a, and ACR levels, indicating that changes in the gut microbiome may directly influence key immunological markers associated with lupus severity. The depletion of beneficial species and the enrichment of potentially pathogenic bacteria appear to contribute to immune activation and disease progression. This study suggests that gut microbiota dysbiosis plays a critical role in exacerbating lupus by modulating immune responses, reinforcing the link between microbial composition and lupus pathogenesis. Our findings provide the first evidence identifying these distinct gut microbial species as potential contributors to lupus severity, highlighting their role as key factors in disease progression.