Analysis of the alleviating effect of modified Huangqi Chifeng decoction on rats with focal segmental glomerulosclerosis based on gut microbiota and fecal metabolomics

Aims To investigate the reno-protective effects of modified Huangqi Chifeng decoction (MHCD) on focal segmental glomerulosclerosis (FSGS) rats, and the underlying mechanisms of systemic regulation of gut microbiota and metabolite profiles.Methods and results A rat FSGS model was established via unilateral nephrectomy plus doxorubicin injections. Rats were divided into sham, FSGS, and MHCD groups from which urine, blood, and histological tests were conducted. Fecal microbiotas were identified via 16S rRNA gene sequencing. Fecal metabolomics allowed for metabolic pathways analysis. Biochemical indices and pathological examination revealed that MHCD treatment improved the symptoms of FSGS, and corrected dysbiosis of gut microbiota, enriched the abundance of Bifidobacterium, Odoribacter, Christensella, Oscillospira, and reduced that of harmful bacteria such as Collinsella and Coprobacterilus at the genus level. Fecal metabolomic profiles revealed 152 different metabolites between the FSGS and sham groups, which are mainly enriched in signaling pathways like arachidonic acid, serotonergic synapse, and oxytocin. Besides, 93 differential metabolites between MHCD and FSGS groups were identified, which are mainly enriched in signaling pathways like steroid hormone biosynthesis, prostate cancer, and linoleic acid metabolism. Spearman's correlation analysis showed a correlation between differential fecal metabolites and enriched gut microbiota or serum biochemical parameters.Conclusions MHCD may exert a reno-protective effect by regulating the gut microbiome and metabolite profiles in FSGS rats.