In the last decade, several studies have demonstrated Cutibacterium acnes colonization in intervertebral discs (IVDs) in patients with lumbar disc degeneration (LDD) and low back pain (LBP), but the meaning of these findings remains unclear. Being aware of this knowledge gap, we are currently conducting a prospective analytical cohort study with LBP and LDD patients undergoing lumbar microdiscectomy and posterior fusion. The IVDs samples collected during the surgeries are subjected to a stringent analytical protocol using microbiological, phenotypic, genotypic, and multiomic techniques. Additionally, pain-related scores and quality-of-life indexes are monitored during patient follow-up. Our preliminary results for 265 samples (53 discs from 23 patients) revealed a C. acnes prevalence of 34.8%, among which the phylotypes IB and II were the most commonly isolated. The incidence of neuropathic pain was significantly higher in the colonized patients, especially between the third and sixth postoperative months, which strongly suggests that the pathogen plays an important role in the chronicity of LBP. The future results of our protocol will help us to understand how C. acnes contributes to transforming inflammatory/nociceptive pain into neuropathic pain and, hopefully, will help us to find a biomarker capable of predicting the risk of chronic LBP in this scenario.