Evidence suggests that intervertebral disc degeneration (IVDD) can be induced by Propionibacterium acnes (P. acnes), although the underlying mechanisms are unclear. In this study, we analyzed the pathological changes in degenerated human intervertebral discs (IVDs) infected with P. acnes. Compared with P. acnes-negative samples, P. acnes-positive IVDs showed increased apoptosis of nucleus pulposus cells (NPCs) concomitant with severe IVDD. Then, a P. acnes-inoculated IVD animal model was established, and severe IVDD was induced by P. acnes infection by promoting NPC apoptosis. The results suggested that P.acnes-induced apoptosis of NPCs via the Toll-like receptor 2 (TLR2)/c-Jun N-terminal kinase (JNK) pathway and mitochondrial-mediated cell death. In addition, P. acnes was found to activate autophagy, which likely plays a role in apoptosis of NPCs. Overall, these findings further validated the involvement of P. acnes in the pathology of IVDD and provided evidence that P. acnes-induced apoptosis of NPCs via the TLR2/JNK pathway is likely responsible for the pathology of IVDD.

Purpose. To investigate whether P. acnes could induce disc degeneration and Modic changes when inoculated into the discs of rabbits. Method. A wild-type strain of P. acnes isolated from a patient associated with Modic change and disc degeneration was inoculated into the intervertebral discs of rabbits. Meanwhile, S. aureus was injected into the discs to establish a model of discitis as the comparison and a standard strain of P. acnes was inoculated as the control. MRI and histological change were observed. Results. Both the P. acnes-inoculated and S. aureus-inoculated rabbits showed hyperintense signals at endplates and hypointense signals at nucleus pulposus on T2WI. However, P. acnes only resulted in moderate disc degeneration and endplates rupture in histological examination, which was different from the pathological change of discitis caused by S. aureus. In addition, higher death rates (2/3 versus 0/5) were observed in S. aureus-inoculated rabbits. Conclusion. Compared to S. aureus, the pathological change caused by P. acnes would be considered as Modic-I change and disc degeneration rather than a discitis.

Latent P. acnes infection was associated with chronic inflammation in degenerated intervertebral discs, especially in the samples with visible bacteria in histology, which manifested as increased numbers of cytokines and neutrophils. Discs with P. acnes infection had much severer disc degeneration and P. acnes-associated chronic inflammation may be the reason.

Propionibacterium acnes (P. acnes), an important opportunistic anaerobic Gram-positive bacterium, causes bone and joint infections, discitis and spondylodiscitis. Accumulated evidence suggested that this microbe can colonise inside intervertebral discs without causing symptoms of discitis. Epidemiological investigation shows that the prevalence ranges from 13 % to 44 %. Furthermore, colonisation by P. acnes inside nonpyogenic intervertebral discs is thought to be one pathogen causing sciatica, Modic changes and nonspecific low back pain. Specially, patients can attain significant relief of low back pain, amelioration of Modic changes and alleviation of sciatica after antibiotic therapy, indicating the role of P. acnes in these pathological changes. However, until now, there were hypotheses only to explain problems such as how P. acnes access intervertebral discs and what the exact pathological mechanism it employs during its latent infection period. In addition, research regarding diagnostic procedures and treatment strategies were also rare. Overall, the prevalence and possible pathological role that P. acnes plays inside nonpyogenic intervertebral discs is summarised in this paper.

Accumulating evidence suggests that Propionibacterium acnes (P. acnes) is a novel pathogenic factor promoting intervertebral disc degeneration (IVDD). However, the underlying mechanisms by which P. acnes induces IVDD have been unclear. In this study, we quantified the severity of IVDD, as well as the expressions of inducible nitric oxide synthase (iNOS)/nitric oxide (NO) and cyclooxygenase (COX-2)/prostaglandin (PGE2) in human intervertebral discs (IVDs) infected with P. acnes. Compared with P. acnes-negative IVDs, P. acnes-positive IVDs showed increased iNOS/NO and COX-2/PGE2 activity concomitant with more severe IVDD. In order to detect the potential correlation between iNOS/NO expression, COX-2/PGE2 expression, and IVDD, we developed a P. acnes-induced IVDD rat model and found that the upregulation of iNOS/NO and COX-2/PGE2 was essential to the occurrence of P. acnes-induced IVDD. This finding was supported by the fact that the inhibition of iNOS/NO and COX-2/PGE2 activity ameliorated IVDD significantly, as evidenced by restored aggrecan and collagen II expression both in vivo and in vitro. Mechanistically, we found that P. acnes induced iNOS/NO and COX-2/PGE2 expressions via a reactive oxygen species- (ROS-) dependent NF-κB cascade. Furthermore, NADPH oxidase participated in P. acnes-induced ROS, iNOS/NO, and COX-2/PGE2 expressions. Overall, these findings further validated the involvement of P. acnes in the pathology of IVDD and provided evidence that P. acnes-induced iNOS/NO and COX-2/PGE2 activation via the ROS-dependent NF-κB pathway is likely responsible for the pathology of IVDD.

Purpose. Low-virulence anaerobic bacteria, especially the Propionibacterium acnes (P. acnes), have been thought to be a new pathogeny for a series of disc diseases. However, until now, there has been no histological evidence to confirm this link. The purpose of this study was to confirm the presence of P. acnes in nonpyogenic intervertebral discs via histological observation. Method. Degenerated intervertebral discs were harvested from 76 patients with low back pain and/or sciatica but without any symptoms of discitis or spondylodiscitis. The samples were cultured under anaerobic conditions and then examined using 16S rDNA PCR to screen for P. acnes. Samples found to be positive for P. acnes were stained with hematoxylin-eosin (HE) and modified Brown-Brenn staining and observed under a microscope. Results. Here, 16 intervertebral discs were found to be positive for P. acnes via 16S rDNA PCR and the prevalence was 21.05% (16/76). Among them, 7 samples had visible microbes stained with HE and modified Brown-Brenn staining. Morphological examination showed the bacteria to be Gram-positive and rod-shaped, so they were considered P. acnes. Conclusion. P. acnes is capable of colonizing some degenerated intervertebral discs without causing discitis, and its presence could be further confirmed by histological evidence. Targeting these bacteria may be a promising therapy method for some disc diseases.

Purpose The role of bacteria, especially Propionibacterium acnes (P. acnes), in human intervertebral disc diseases has raised attention in recent years. However, limited sample size of these studies and diverse bacteria-positive proportion made this topic still controversial. We aimed to review related articles and summarize the bacteria-positive proportion in these studies. Methods We searched the PubMed, Cochrane Library, Embase for related literature from January 2001 to May 2018, and the reference articles were also searched. The random effects or fixed effects meta-analysis was used to pool the overall positive proportion or odds ratio of these studies. ResultsWe found 16 relevant articles and 2084 cases of the bacteria culture from surgery. Within the 16 included studies, 12 studies' results supported the infection in the discs. The pooled bacterial infection rate was 25.3%. The pooled P. acnes infection rate was 15.5%. The overall pooled P. acnes proportion in bacteria-positive discs was 56.4%. We also found that the presence of bacteria may contribute to the development of Modic change with the odds ratio as 1.27 (95% CI: 0.44-3.64), but this result is not significant due to heterogeneity, so further study is needed. Conclusion The existence of bacteria in the intervertebral discs was proved by many studies. However, the variety in sample collecting and culture methods is still obvious and the positive rate also fluctuated within the studies. Standardized and reliable methods should be taken to promote the study in the future. Graphic abstractThese slides can be retrieved under Electronic Supplementary Material.

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