ABSTRACT Background Chronic low back pain (LBP) is the leading cause of disability worldwide, yet its underlying pathophysiology remains poorly understood. Current diagnostic techniques rely heavily on imaging, which is insufficient for identifying inflammatory or systemic contributors. Emerging evidence suggests a role for gut microbiome dysbiosis in inflammatory pain pathways, yet its specific contribution to chronic LBP remains unclear. The aim of this study is to investigate gut microbiome alterations in chronic LBP patients compared to healthy controls. Methods Twenty‐eight patients with chronic LBP (> 3 months) without advanced disk degeneration (Pfirrmann grade < 4) and 28 age‐, sex‐, and BMI‐matched healthy controls were recruited. Stool samples were analyzed using 16S rRNA V4 gut microbiome analysis. Alpha diversity and beta diversity were assessed to determine microbial diversity differences. Taxonomic composition was compared at the phylum and genus levels. Results There were no significant differences in age, sex, BMI, and race between the two groups. Patients with chronic LBP exhibited significantly reduced alpha diversity compared to controls ( U = 517, p = 0.003, r = 0.395). Beta diversity analysis demonstrated distinct clustering between groups, suggesting significant shifts in microbial composition (PERMANOVA, p < 0.05). At the phylum level, Proteobacteria ( U = 91, p < 0.001, r = 0.659) and Desulfobacterota ( U = 73, p < 0.001, r = 0.718) were significantly elevated in chronic LBP patients, while Bacteroidota was significantly reduced ( U = 524, p = 0.031, r = 0.289). At the genus level, Prevotella ( U = 272, p = 0.045, r = 0.268) and Faecalibacterium ( U = 254, p = 0.024, r = 0.302) were increased in chronic LBP patients, whereas Parabacteroides was depleted ( U = 621, p < 0.001, r = 0.500). Conclusion These findings indicate that gut microbiome dysbiosis may play a key role in chronic LBP among patients without identifiable surgical pathologies, likely through systemic inflammation, reinforcing the “gut–disk axis” hypothesis. Given the limitations of conventional diagnostic tools and management strategies, microbiome profiling may provide novel biomarkers for LBP and inform microbiome‐targeted therapies such as probiotics, dietary modifications, and fecal microbiota transplantation. Future research should explore causal relationships and strain‐specific microbial effects to refine microbiome‐based interventions for chronic LBP.
Sima et al. (Tue,) studied this question.