Gut-spine axis: a possible correlation between gut microbiota and spinal degenerative diseases

Abstract

As society ages, the number of patients with spinal degenerative diseases (SDD) is increasing, posing a major socioeconomic problem for patients and their families. SDD refers to a generic term for degenerative diseases of spinal structures, including osteoporosis (bone), facet osteoarthritis (joint), intervertebral disk degeneration (disk), lumbar spinal canal stenosis (yellow ligament), and spinal sarcopenia (muscle). We propose the term "gut-spine axis" for the first time, given the influence of gut microbiota (GM) on the metabolic, immune, and endocrine environment in hosts through various potential mechanisms. A close cross-talk is noted between the aforementioned spinal components and degenerative diseases. This review outlines the nature and role of GM, highlighting GM abnormalities associated with the degeneration of spinal components. It also summarizes the evidence linking GM to various SDD. The gut-spine axis perspective can provide novel insights into the pathogenesis and treatment of SDD.

Keywords: gut dysbiosis; gut microbiota; gut-bone axis; gut-spine axis; inflammation; spinal degenerative disease.

Figure 1

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.

Figure 2

Gut dysbiosis and spinal degenerative diseases. Gut dysbiosis and SDD have common risk factors and treatments that can interact with each other. OPLL, ossification of the posterior longitudinal ligament; DISH, diffuse idiopathic skeletal hyperostosis.

Figure 3

Example of thoracic ossification of the posterior longitudinal ligament (OPLL) in a 53-year-old obese male with type 2 diabetes mellitus. The spinal canal is markedly narrowed by thoracic OPLL, with inability to walk. (A) Sagittal computed tomography (CT) of the whole spine. (B) Sagittal CT of the thoracic spine. This is a case from our institution.

Figure 4

Myelography computed tomography (CT) in lumbar axial view. The red arrow indicates facet degeneration and osteophyte. This is a case from our institution.

Figure 5

T2-weighted magnetic resonance imaging (MRI) sagittal image of the lumbar spine. The green arrowhead indicates normal intervertebral disk, the yellow arrowhead indicates intervertebral degenerated disk, and the white arrowhead indicates hypertrophic yellow ligament. This is a case from our institution.