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Intervertebral disc degeneration (IVDD) is a prevalent orthopedic condition with lower back pain as the predominant clinical presentation that challenges clinical treatment with few therapeutic options. Duhuo Jisheng Decoction (DHJSD) has been proven effective in the therapy of IVDD, but the precise underlying mechanisms remain not fully elucidated. The current study was designed to test our hypothesis that DHJSD may systematically correct the phenotypic disruption of the gut microbiota and changes in the serum metabolome linked to IVDD. Analysis of the active ingredients of DHJSD by ultra high performance liquid chromatography. An integrated metagenomic and metabonomic approach was used to analyze feces and blood samples from normal and IVDD rats. Compared to the control group, fiber ring pinning on the caudal 3 to caudal 5 segments of the rats caused IVDD and significantly altered the compositions of the intestinal microbiota and serum metabolites. Integrated analysis revealed commonly-altered metabolic pathways shared by both intestinal microbiota and serum metabolome of the IVDD rats. DHJSD inhibited the degenerative process and restored the compositions of the perturbed gut microbiota, particularly the relative abundance of commensal microbes of the Prevotellaceae family. DHJSD also corrected the altered metabolic pathways involved in the metabolism of glycine, serine, threonine, valine, the citric acid cycle, and biosynthesis of leucine and isoleucine. DHJSD inhibited the disc degeneration process by an integrated metagenomic and metabonomic mechanism to restore the microbiome profile and normalize the metabonomic pathways.