High fat diet-induced diversity reduction in gut microbiota facilitates the development of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is influenced by environmental, genetic, and dietary factors. The impact of a high-fat diet (HFD) on SLE pathogenesis remains unclear. To investigate this, we utilized an imiquimod (IMQ)-induced SLE mouse model under HFD and normal diet conditions. Mice receiving both HFD and IMQ exhibited aggravated inflammation, tissue damage, and enhanced B-cell infiltration in the colon, alongside significant reductions in gut microbial diversity. Notably, HFD alone induced similar microbiome and immune alterations, suggesting a pro-SLE intestinal microenvironment. Microbiome analysis identified specific species shifts, including Parabacteroides goldsteinii and Bacteroides caccae, associated with disease progression. Metabolomic profiling revealed dysregulation of several pathways, including amoebiasis, with marked reduction of dl-o-phosphoserine. These findings suggest that HFD-induced microbial and metabolic changes may exacerbate SLE development. Our study highlights the interplay between diet, gut microbiota, and immune regulation in SLE, providing potential targets for microbiome- or diet-based interventions.