Gut-Intervertebral Disc Axis: Gut Microbiome-Driven Immune-Metabolic Imbalance and Intervertebral Disc Degeneration

Intervertebral disc degeneration (IDD) serves as a critical structural basis for chronic low back pain, severely impairing patients' quality of life and imposing a significant socioeconomic burden. Current interventions remain largely limited to symptomatic treatments including pharmacological analgesia and surgical intervention. The recently proposed "gut-disc axis" suggests that the gut microbiome can reshape the endplate-disc microenvironment by influencing intestinal barrier integrity, microbial metabolite profiles, and host immune-metabolic status. Existing evidence indicates that dysbiosis-related increases in endotoxin load, dysregulated metabolism of short-chain fatty acids, tryptophan, and bile acids, systemic low-grade inflammation, and shifts in immune cell lineages may collectively promote nucleus pulposus cell senescence and apoptosis, matrix degradation, and endplate pathology. Mendelian randomization studies have also suggested potential causal links between certain gut microbiota and disc diseases. However, the determination of whether "microbial signals" detected within the intervertebral disc represent true colonization is currently hindered by methodological limitations, particularly low-biomass contamination. This review focuses on mechanisms through which gut microbiota influence the endplate-disc microenvironment via immune-metabolic pathways, including the LPS/TLR4/NF-κB axis, SCFAs-AhR axis, and lipid/iron metabolism, while only briefly addressing studies related to mechanical injury and surgery. Building on these insights, we integrate advances from clinical cohorts, animal models, and multiomics studies, summarize key actionable intervention nodes, and propose a preliminary patient stratification framework and validation pathway based on gut-immune-metabolic typing, providing a theoretical foundation for developing microbiome-guided disease-modifying interventions.