Subclinical Infection and Disc Dysbiosis as a Cause of Degenerative Disc Disease and Low Back Pain

Abstract

Background: To document the role of sub-clinical infection in disc disorders and investigate the existence of a microbiome in healthy, herniated, and degenerated intervertebral discs (IVD) through next generation genomics tools. Methods: Genomic DNA from 24 lumbar IVDs (8 MRI normal discs (ND) from brain dead yet alive organ donors, 8–Disc herniation (DH), 8–Disc degeneration (DD)) were subjected to 16S rRNA sequencing using the Illumina MiSeq platform for profiling the diversity of human disc microbiome in health and disease. Mass spectrometric analysis was performed to reconfirm the presence of conserved bacterial proteins. The disc microbiome was compared to established human gut and skin microbiomes to identify common microorganisms. Findings: All healthy MRI normal discs from brain dead yet alive organ donors also had a rich bacterial presence. A total of 424 different species (355-ND, 346-DD, and 322-DH) were detected in all 24 samples, with 42·75% OTUs being classified at the Kingdom level, 44% at the Phylum level, 22·62% at the Genus level, and 5·5% at Species level. Varying biodiversity and abundance between the healthy and diseased discs were documented with protective bacteria being abundant in normal discs, and putative pathogens abundant in DD and DH. Propionibacterium acnes had a similar but lower abundance to other pathogens in all three groups ND (3·07%), DD (3·88%), DH (1·56%). Forty-eight bacteria were common between Gut/IVD microbiome, 23 between skin/IVD microbiome, and three common to gut/skin/IVD. Interpretation: Our study challenges the hitherto concept of sterility in healthy IVD and documented an established microbiome even in MRI normal healthy discs. The varying abundance of bacteria between ND, DD, and DH documents ‘Dysbiosis’ as a possible etiology of DD. Many known pathogens were identified in greater abundance than Propionibacterium acnes, and there was evidence for the presence of the Gut- Skin- Spine microbiome axis. Funding Statement: The project was mainly funded by Ganga Orthopaedic Research & Education Foundation (GOREF 2018-08) and partially by the AO Spine (AOSIN(R) 2017-04). Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: The study was performed only after approval of the IRB committee.