The intervertebral disc is a complex structure composed of the central nucleus pulposus, the peripheral annulus fibrosus, and the cartilaginous endplates located at the top and bottom. This unique arrangement effectively isolates the nucleus pulposus from the host’s immune system. Additionally, specific substances within the intervertebral disc exhibit inhibitory effects on the infiltration of immune cells and cytokines, which has led to the recognition of the intervertebral disc as an immune-privileged tissue. However, during intervertebral disc degeneration (IDD), the physical barriers that maintain this immune privilege are compromised. As a result, the nucleus pulposus may be perceived as a foreign antigen by the immune system. Simultaneously, inflammatory cytokines released by the degenerating disc attract a significant influx of immune cells, disrupting the delicate immunological balance within the nucleus pulposus and exacerbating the progression of IDD. Recent studies have confirmed the infiltration of immune cells such as macrophages and mast cells into the degenerative intervertebral disc, and the phenotypic characteristics and quantitative changes of these immune cells are closely related to the process of IDD. In terms of treatment strategies, biological agents such as mesenchymal stem cell therapy, gene therapy and growth factors that regulate the immune microenvironment of degenerative intervertebral discs have entered the stage of animal experiments. At the same time, small molecule drugs have shown unique regulatory potential in restoring the immune-privileged status of intervertebral discs.

The intervertebral disc is a complex structure composed of the central nucleus pulposus, the peripheral annulus fibrosus, and the cartilaginous endplates located at the top and bottom. This unique arrangement effectively isolates the nucleus pulposus from the host’s immune system. Additionally, specific substances within the intervertebral disc exhibit inhibitory effects on the infiltration of immune cells and cytokines, which has led to the recognition of the intervertebral disc as an immune-privileged tissue. However, during intervertebral disc degeneration (IDD), the physical barriers that maintain this immune privilege are compromised. As a result, the nucleus pulposus may be perceived as a foreign antigen by the immune system. Simultaneously, inflammatory cytokines released by the degenerating disc attract a significant influx of immune cells, disrupting the delicate immunological balance within the nucleus pulposus and exacerbating the progression of IDD. Recent studies have confirmed the infiltration of immune cells such as macrophages and mast cells into the degenerative intervertebral disc, and the phenotypic characteristics and quantitative changes of these immune cells are closely related to the process of IDD. In terms of treatment strategies, biological agents such as mesenchymal stem cell therapy, gene therapy and growth factors that regulate the immune microenvironment of degenerative intervertebral discs have entered the stage of animal experiments. At the same time, small molecule drugs have shown unique regulatory potential in restoring the immune-privileged status of intervertebral discs.

Discogenic low back pain from intervertebral disc degeneration was one of the major public health problems in the world, leading to global workforce decline. Recent studies showed that microorganisms existed in the intervertebral disc with significant differences between the normal intervertebral disc and the degenerated ones in not only species and numbers but also the changes of their functional activities. In addition, there was an overlap in microbial populations between the gut and the intervertebral disc, suggesting that the gut microbiota may play a key role in the pathological process of intervertebral disc degeneration. To further explore the relationship between gut microbiota and the host immune metabolic system, the concept of gut-organ axis was established. Researchers proposed the theory of gut-intervertebral disc axis to clarify the specific mechanism of intestinal flora in intervertebral disc degeneration. Studies showed that microorganisms could enter the intervertebral disc in a variety of ways, such as hematogenous transmission, lymphatic route, and invasion through annulus fibrosus tears. The arrival of these microorganisms in the intervertebral disc would trigger a series of local immune and inflammatory responses, promoting the degeneration of the intervertebral disc tissue. In the future, precision medical strategies targeting the gut and intervertebral disc microbiome may become promising in the prevention and treatment of intervertebral disc degeneration. With further research in this field, the treatment of intervertebral disc degeneration by targeting the gut and intervertebral disc microbiota showed great clinical value. This article reviewed and discussed the effect of intestinal flora imbalance on intervertebral disc degeneration and the potential therapeutic effect of adjusting intestinal flora on intervertebral disc degeneration. The theory of gut-intervertebral disc axis, which provided a new perspective to understand the pathogenesis of intervertebral disc degeneration, supported innovative treatment methods in the future.

Discogenic low back pain from intervertebral disc degeneration was one of the major public health problems in the world, leading to global workforce decline. Recent studies showed that microorganisms existed in the intervertebral disc with significant differences between the normal intervertebral disc and the degenerated ones in not only species and numbers but also the changes of their functional activities. In addition, there was an overlap in microbial populations between the gut and the intervertebral disc, suggesting that the gut microbiota may play a key role in the pathological process of intervertebral disc degeneration. To further explore the relationship between gut microbiota and the host immune metabolic system, the concept of gut-organ axis was established. Researchers proposed the theory of gut-intervertebral disc axis to clarify the specific mechanism of intestinal flora in intervertebral disc degeneration. Studies showed that microorganisms could enter the intervertebral disc in a variety of ways, such as hematogenous transmission, lymphatic route, and invasion through annulus fibrosus tears. The arrival of these microorganisms in the intervertebral disc would trigger a series of local immune and inflammatory responses, promoting the degeneration of the intervertebral disc tissue. In the future, precision medical strategies targeting the gut and intervertebral disc microbiome may become promising in the prevention and treatment of intervertebral disc degeneration. With further research in this field, the treatment of intervertebral disc degeneration by targeting the gut and intervertebral disc microbiota showed great clinical value. This article reviewed and discussed the effect of intestinal flora imbalance on intervertebral disc degeneration and the potential therapeutic effect of adjusting intestinal flora on intervertebral disc degeneration. The theory of gut-intervertebral disc axis, which provided a new perspective to understand the pathogenesis of intervertebral disc degeneration, supported innovative treatment methods in the future.