Perturbed microbial ecology in pediatric systemic lupus erythematosus: Evidence from the gut microbiome and serum metabolome

Pediatric systemic lupus erythematosus (pSLE) is a debilitating autoimmune disease. Emerging evidence indicates that the gut microbiome plays a key role in maintaining immune system homeostasis. However, how alterations in the gut microbiome and associated metabolic profiles contribute to the development and severity of pSLE remains unclear. Here, we report that pSLE exhibits decreased α-phylogenetic diversity and significant disruptions in both the gut microbiome and serum metabolome. Specific microbial taxa were closely associated with disease severity. Streptococcus salivarius levels were notably elevated, nearly quadrupled, in patients with active pSLE or lupus nephritis compared with healthy individuals. The streptococcus-dominant microbial disturbance matches findings in adult SLE. pSLE patients also exhibited a simplified and disrupted gut microbial network with reduced ecological complexity; furthermore, a combination of microbial markers effectively distinguished pSLE from healthy controls with 91.6% accuracy. Untargeted serum metabolomics revealed metabolic profile alterations in pSLE, including widespread dysregulation of lipids and tryptophan metabolism. Moreover, a single serum metabolite marker, such as omphalotin B or PI(16:0/20:2(11Z,14Z)), achieved an even higher accuracy of 97%. The altered gut microbial composition is associated with serum metabolome changes. A strong correlation between PI(16:0/20:2(11Z,14Z)) and Streptococcus anginosus abundance suggests potential microbiota-metabolite interactions. Collectively, these data demonstrate disturbances in microbiome composition and activity that are likely to be relevant to the pathogenesis of pSLE.