Perturbed gut microbiota and serum metabolites are associated with progressive renal fibrosis.

Introduction: The intricate pathogenesis of renal fibrosis necessitates identifying biomarkers at various stages to facilitate targeted therapeutic interventions, which would enhance patient survival rates and significantly improve prognosis.

Methods: We investigated the changes in gut microbiota and serum metabolites during the early, middle, and late stages of renal fibrosis in rats using 16S rDNA sequencing and UPLC-QTOF/MS-based metabolomics.

Results: We identified 5, 21, and 14 potential gut microbial markers and 19, 23, and 31 potential metabolic markers in the MOD1, MOD2, and MOD4 groups, respectively. Bifidobacterium was identified as a shared microbial marker between the MOD1 and MOD2 groups; Prevotellaceae_NK3B31_group and Bacteroides were identified as shared microbial markers between the MOD2 and MOD4 groups. The pathways of arachidonic acid metabolism and retinol metabolism were found to play a significant role in the modulation of renal fibrosis at 1, 2, and 4 weeks. Notably, the metabolic biomarkers 8,9-EET and 5(S)-HPETE within these pathways emerged as critical determinants influencing renal fibrosis.

Discussion: Our findings demonstrated that the severity of renal fibrosis is associated with dysbiosis of the gut microbiota and alterations in serum metabolites.