Different phylotypes of Cutibacterium acnes cause different modic changes in intervertebral disc degeneration

Abstract

Background: The contribution of Cutibacterium acnes (C. acnes) infection to intervertebral disc degeneration (IDD) and the antibiotic therapy has evoked several controversies in recent years. While some microbiology studies report bacterial disc infection within IDD patients, others attribute the positive results to contamination during prolonged cultures. In addition to the clinical controversy, little was known about the mechanism of C. acnes-caused Modic changes (MCs) if C. acnes was the pathogenic factor.

Objectives: This study aimed to investigate the inflammatory mechanism of MCs induced by different phylotypes of C. acnes in patients with IDD.

Methods: Specimens from sixty patients undergoing microdiscectomy for disc herniation were included, C. acnes were identified by anaerobic culture, followed by biochemical and PCR-based methods. The identified species of C. acnes were respectively inoculated into the intervertebral discs of rabbits. MRI and histological change were observed. Additionally, we detected MMP expression in the rabbit model using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

Results: Of the 60 cases, 18 (30%) specimens were positive for C. acnes, and we identified 4 of 6 defined phylogroups: IA, IB, II and III. The rabbits that received Type IB or II strains of C. acnes showed significantly decreased T1WI and higher T2WI at eighth weeks, while strain III C. acnes resulted in hypointense signals on both T1WI and T2WI. Histological examination results showed that all of the three types of C. acnes could cause disc degeneration and endplates rupture. Moreover, endplate degeneration induced by type IB or II strains of C. acnes is related with MMP13 expression. Meanwhile, strain III C. acnes might upregulated the level of MMP3.

Conclusion: This study suggested that C. acnes is widespread in herniated disc tissues. Different types of C. acnes could induce different MCs by increasing MMP expression.

Fig 1. Signal changes were observed at the second week after the inoculation of the isolated three types strain of C. acnes.

Before the surgery, there were no abnormal signals at T1WI and T2WI. An obvious hypointense signal was observed on T1WI and the hyperintense signal was found on T2WI at the C. acnes-inoculated segment (L5-L6, indicated by a white filled arrow) in Group I and Group II. The hypointense signal changes were also observed on T1WI in the rabbits of Group III, while the signal intensity of T2WI decreased in this group animals. No significant signal changes were observed at the internal control segment of L4-L5 in all groups (indicated by a thin arrow).

Fig 2. Typical histological images of slices from the three groups of rabbits at eighth weeks after the inoculation.

The intervertebral discs from the TSB-inoculated control segment (L4-L5) had distinct nucleus pulposus and normal arranged annulus fibrosus. The segment of three types of C. acnes inoculated intervertebral discs (L5-L6) was demonstrated as disappearance of nucleus pulposus, endplates fracture (black rectangle), disorganized annulus fibrosus, and partly cartilage proliferation.

Fig 3. RT-qPCR analysis of MMP13 and MMP1 mRNA expression in endplate chondrocytes cocultured with 2% or 4% supernatant of different phylotypes of C.acnes.

*p < 0.05, **p < 0.01.