Background: Modic changes (MCs), vertebral end plate and bone marrow damage observed by magnetic resonance imaging, are an independent risk factor for low back pain. The compositions of and interaction between microbiota and metabolites in the lumbar cartilaginous end plates (LCEPs) of patients with MCs have not been identified. Methods: Patients with lumbar disc degeneration who were undergoing lumbar spinal fusion surgery were recruited between April 2020 and April 2021. LCEPs were collected for 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC/MS)-based targeted metabolomic profiling. Of the 54 patients recruited, 24 had no MCs and 30 had changes classified as Modic type 2 or 3. The primary goal was to identify specific genera of microbiota associated with MCs, and secondary goals included investigating differences in metabolites between patients with and without MCs and exploring the correlation between these metabolites and microorganisms. Results: Investigation of the microbiota community structure revealed that both alpha diversity and beta diversity were significantly different between patients with and without MCs, and the abundances of 26 genera were significantly different between these 2 groups. Metabolomic analysis revealed that 26 metabolites were significantly different between the 2 groups. The unsaturated fatty acid pathway was found to be the main pathway related to MCs. Multiomic correlation analysis suggested that Caulobacteraceae (unclassified) and Mycobacterium, Clostridium, Blautia, and Bifidobacterium at the genus level were linked to dysregulation of fatty acid metabolism, contributing to the pathogenesis of MCs. Conclusions: Our study represents a foundational effort to examine the landscape of the microbiota and metabolites in patients with MCs, informing future studies on the pathogenesis of and targeted therapy for MCs. Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.