The gut-spine axis: a model of intestinal epithelial damage signaling that may regulate degeneration of spinal structures. (A) Gut microbiota and dysbiosis: GM supplies the host with essential functions such as the synthesis of short-chain fatty acids (SCFA), vitamins, nutrients, and neurotransmitters (including some precursor substances). When leaky gut syndrome occurs, which results in altered GM composition and GM dysbiosis, the intestinal barrier is compromised, altering physiological and metabolic functions and disrupting immune, endocrine, vascular, and nervous system responses, resulting in bacteremia, bacterial-derived compounds (LPS), and cytokines circulating along the bloodstream to systemic tissues. (B) Spinal degenerative diseases (SDD): osteoporosis, IVDD, facet OA, and LSS. GM dysbiosis-derived metabolites, bacteremia, and inflammatory cytokines can result in local and systemic responses that may cause SDD. This figure was adapted and modified from the figure by Li et al. (2022) and was created using BioRender.com. This content is available under Creative Commons Attribution 4.0 International License (https://link.springer.com/article/10.1007/s00586-022-07152-8). IVDD, intervertebral disk degenerative disease; OA, osteoarthritis; LSS, lumbar spinal canal stenosis; SCFA, short-chain fatty acids; LPS, lipopolysaccharide.