Oral Presentation 51st International Society for the Study of the Lumbar Spine Annual Meeting 2025

Introduction: Modic changes (MC) are associated with endplate damage, neoinnervation, and chronic low back pain (cLBP). Although the precise etiology of MC is unclear, growing evidence points to the important role of disc/vertebra crosstalk resulting in either adaptive or innate immune responses. An unexplored potential contributor to MC is the gut microbiome. This microbial community is key in modulating immune and inflammatory responses. For example, gut commensals impact the activation threshold for pathogenic stimuli by producing metabolites that modulate cytokine production and induce T-cell expansion. This study aimed to discover new linkages between the gut microbiome and MC in patients with cLBP.

Methods: Stool samples from 37 patients with cLBP (>3-month duration) were included in this prospective study. 3T MRI of the lumbar spine included sagittal T₁- and fat-saturated T₂-weighted sequences to diagnose MC: no MC (MC0, n=20 patients); MC1 with bone marrow edema-like signal along the endplates (n=17 patients). Stool samples were collected within 2-3 weeks of MRI and frozen until analysis. DNA was extracted from the samples, and PCR amplification of the 16S rRNA gene was performed. Bacterial reads were filtered, denoised, and merged. Taxonomic classifications were assigned, and sequence variants were combined and representatively rarefied to 12,428 reads per sample. Measures of within-sample taxonomic diversity (α-diversity) included Chao1, Shannon diversity index, Faith’s phylogenetic diversity, and Pileou’s evenness index, and were compared between patients with MC0 and MC1 using a Wilcoxon rank-sum test. Measures of between-sample compositional similarity (β-diversity) included unweighted UniFrac distances and were compared for group differences using PERMANOVA. p<0.05 was considered significant.

Results: There were no significant differences in age, sex, or BMI between patients with vs. without MC1(p>0.05). Measures of α-diversity were significantly higher in patients with MC1 than MC0 (Chao1 p=0.004, Shannon p=0.004, Faith p=0.003, Figure 1). PERMANOVA revealed significant differences in microbial community compositions between MC0 and MC1 patients for most β-diversity measures (Unweighted UniFrac R²=0.071, p=0.002). Differential relative abundance analysis (Figure 2) identified 22 taxa that were significantly higher in patients with MC1, including increased abundance of pro-inflammatory bacteria (e.g., Prevotella, Bacteroidales) and anti-inflammatory bacteria (e.g., Oscillospirales, Coprococcus). Patients with MC0 had a higher abundance of anti-inflammatory Lachnospiraceae and Bacteroides.

Discussion: There were significant differences in gut microbial α-diversity and β-diversity measures between MC0 and MC1 patients. MC1 patients exhibited a more diverse fecal microbiota and were highly enriched for Oscillospirales, Coprococcus and Lachnospiraceae, amongst others. In contrast, MC0 patients had enrichment of a distinct Lachnospiraceae member indicating that species or strain-specific differences in bacteria in the feces of these patients relate to MC status. These differences indicate that the fecal microbiota may potentially reflect or contribute to differing immune and/or inflammatory responses related to MC presence in the lumbar spine.

Acknowledgment: The authors are indebted to the University of California San Francisco (UCSF) Benioff Center for Microbiome Medicine Microbial Genomics CoLab Plug-in for their assistance in microbiome data generation and analysis.