Renal mRNA sequencing of SLE mouse model treated with Qihuang Jianpi Zishen decoction

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus in which immune dysregulation, metabolic reprogramming and gut dysbiosis converge on the kidney. Qihuang Jianpi Zishen decoction (JPZS), a spleen- and kidney-tonifying prescription used in traditional Chinese medicine, has shown renal protective effects, but its metabolism-centred modes of action remain unclear. Here, we combined an MRL/lpr lupus-prone mouse model with multi-omics profiling to delineate how JPZS modulates the gut–kidney axis. Female MRL/lpr mice were randomised to JPZS or vehicle, with C57BL/6 mice as healthy controls. Renal outcomes, serological autoimmunity and immune-inflammatory indices were assessed alongside 16S rRNA sequencing of faecal microbiota, untargeted serum metabolomics and renal transcriptomics, followed by integrative network analyses and targeted validation of glycolytic pathways. JPZS markedly alleviated proteinuria, serum creatinine elevation, glomerular IgG deposition and histopathological damage, and partially normalised circulating cytokines in MRL/lpr mice. JPZS reshaped lupus-associated gut dysbiosis, prominently enriching Akkermansia and restoring microbial pathways linked to carbohydrate metabolism. Concordantly, JPZS remodelled serum metabolites involved in amino-acid and central carbon metabolism and dampened a renal glycolytic gene signature centred on hexokinase 3 (HK3). Targeted assays confirmed reduced renal lactate content, a lower lactate/pyruvate ratio and down-regulation of HK3 and Ldhal6b after JPZS treatment. These findings indicate that JPZS ameliorates lupus nephritis, at least in part, by enriching Akkermansia and suppressing HK3-driven glycolysis in the kidney, highlighting a metabolism-focused mechanism linking a traditional formula to the gut–kidney axis.