Molecular Mechanisms of Intervertebral Disc Degeneration Induced by Propionibacterium acnes.

Intervertebral disc degeneration (IVDD), a prevalent degenerative disorder with substantial socioeconomic impacts, is closely linked to endplate inflammation and chronic low back pain. Its pathogenesis involves multifactorial mechanisms, including long-term chronic mechanical loading, external trauma, and hereditary factors. Emerging evidence highlights Propionibacterium acnes (P. acnes), a gram-positive bacterium with potent proinflammatory properties, as a key contributor to IVDD progression. This review systematically analyses the latest literature on related studies, focusing on the molecular mechanisms of IVDD induced by P. acnes. Three molecules play an important role in the induction of IVDD by P. acnes, namely, IL-1β, MIF, and MMP. In addition, P. acnes induces IVDD through three core mechanisms, namely, proinflammatory (activation of TLR2, production of large amounts of ROS to promote inflammation), pyroptosis (production of large amounts of NLRP3 through the TXNIP-NLRP3 axis and the ROS-NLRP3 axis), and apoptosis (promotion of Bax and inhibition of Bcl-2 expression through the TLR2-JNK pathway). The dissection of these related important molecules and pathogenic mechanisms can lead to a better understanding of the role of P. acnes in IVDD. It can provide an important theoretical basis for future research. However, the current study's lack of large-scale clinical validation, unresolved colonization controversies, and limited experimental methods are limitations. Therefore, in the future, it is still necessary to improve the relevant theories and resolve the current controversies through more advanced experimental methods and higher quality clinical studies. In conclusion, the study of P. acnes-induced IVDD is promising, and further research can be conducted in the future, which is expected to develop novel therapeutic approaches for P. acnes, thus effectively slowing down the development of IVDD.