The Effect of Gut Microbiota on the Progression of Intervertebral Disc Degeneration

Abstract

Objective Intervertebral disc degeneration (IDD) is the main cause of back pain, and its treatment is a serious socio‐economic burden. The safety and treatment of fecal microbiota transplantation (FMT) has been established. However, the relationship between FMT and IDD still unclear. We aimed to explore whether FMT plays a role in IDD to provide a reference for the treatment of IDD. Methods An experimental model of IDD was established using 2‐month‐old male Sprague–Dawley rats. FMT was performed by intragastric gavage of IDD rats with a fecal bacterial solution. Rat serum, feces, and vertebral disc tissue were collected after surgery for 2 months. The levels of TNF‐α, IL‐1β, IL‐6, matrix metalloproteinase (MMP)‐3, MMP‐13, Collagen II, and aggrecan in the serum or vertebral disc tissue were measured by an enzyme‐linked immunosorbent assay, immunohistochemistry, quantitative real‐time polymerase chain reaction, or western blotting. We also examined the pathology of the vertebral disc tissue using hematoxylin and eosin (HE) and safranin O‐fast green staining. Finally, we examined the gut microbiota in rat feces using 16 S rRNA gene sequencing. Results We found that the expression of TNF‐α, IL‐1β, IL‐6, MMP‐3, MMP‐13, NLRP3 and Caspase‐1 increased in the IDD group rats. In contrast, Collagen II and aggrecan levels were downregulated. Additionally, vertebral disc tissue was severely damaged in the IDD group, with disordered cell arrangement and uneven safranin coloration. FMT reversed the effects of IDD modeling on these factors and alleviated cartilage tissue damage. In addition, FMT increased the gut microbiota diversity and microbial abundance in rats treated with IDD. Conclusion Our findings suggest that FMT has a positive effect in maintaining cellular stability in the vertebral disc and alleviating histopathological damage. It affects the diversity and abundance of gut microbiota in rats with IDD. Therefore, FMT may serve as a promising target for amelioration of IDD.

Gut microbiota and intervertebral disc degeneration: a bidirectional two-sample Mendelian randomization study

“…In the mouse model of IVDD, the abundance of Muribaculaceae and Lactobacillus increased, while the abundance of Clostridia_UCG-014 decreased. Furthermore, fecal microbiota transplantation further increased the abundance of Lactobacillus and reduced the abundance of Clostridia_UCG-014 [ 58 ]. Su et al [ 59 ] conducted a Mendelian randomization study on the potential causal effects of specific gut microbiota and gut microbiota metabolites on low back pain (LBP).…”

Genetically predicted causal effects of gut microbiota on spinal pain: a two-sample Mendelian randomization analysis

“…Research on the relationship between gut microbiota and low back pain or/and lower limb pain is more abundant. Yao et al (2023) found a significant decrease in Lachnospiraceae NK4A136 group , Turicibacter , and Roseburia in the feces of rats in a LBP model compared to the control group. In various LBP animal models, Wang et al (2021) also found lower abundance of Lachnospiraceae NK4A136 group in rats with lumbar disk herniation compared to the control group.…”

Changes in the composition of the fecal metabolome and gut microbiota contribute to intervertebral disk degeneration in a rabbit model

“…Thus, it would be intriguing to further establish the disk and skin microbiomes and compare the common or divergent bacteria to the gut microbiota for the evidence of the gut/skin/spine microbiome axis. Clinical testing has uncovered ~ 60 overlapping bacterial strains between the intestine and the IVD [ 22 ]. It also remains to be explored if regulating the intestinal microbiota can impact the diversity and abundance of IVD microbiota and alter IDD.…”

“…Additionally, diversities in eukaryotic viruses and prokaryotic phages have been observed in humans [ 6 ], and further elucidation of the IDD-associated microbiome may shed light on microbial ecology in the gut and IVD of LBP patients. Intriguingly, FMT was recently performed in a Sprague–Dawley rat IDD model by gavage with fecal bacterial solution and increased the intestinal microbial diversity and abundance, reversed the IDD modeling, and ameliorated the damage to IVD tissue [ 22 ]. Increasing evidence suggests that the impairment of some gut microbiota and the metabolite composition can be used as a biomarker for identifying disease progression.…”