Identification of specific gut microbes and their therapeutic potential in ameliorating systemic lupus erythematosus in a mouse model

Aims: The gut microbiome significantly influences autoimmune diseases, including systemic lupus erythematosus (SLE). This study aimed to characterize the gut microbiome and metabolome in SLE and evaluate the therapeutic potential of specific microbial supplementation in MRL/lpr mice. Materials and methods: MRL/lpr mice, a well-established model for SLE, were used to analyze gut microbiome changes before and after SLE symptom onset. 16S rRNA sequencing and GC–MS-based metabolic profiling were performed to identify key microbial species and associated metabolites. Selected microbes were supplemented in MRL/lpr mice for 10 weeks, and their effects on SLE symptoms and Th17/Treg balance were evaluated. Key findings: Eisenbergiella massiliensis, Lacrimispora saccharolytica, and Hungatella xylanolytica were significantly decreased in MRL/lpr mice following the onset of SLE symptoms. These microbes were strongly correlated with specific metabolites, including 5-cholestanol, cholesterol, p-cresol, and indole. Supplementation with these microbes alleviated SLE symptoms and modulated the Th17/Treg balance. Significance: This study highlights the critical role of gut microbiota in immune regulation and SLE symptom relief. Targeted microbial supplementation may serve as a novel therapeutic strategy for managing SLE.