GUT MICROBIOME DYSBIOSIS IN CHRONIC LOW BACK PAIN: A LARGE-SCALE METAGENOMIC ANALYSIS IN TWINSUK

Conflicts of Intertest: No conflicts of interest Sources of Funding: CDRF grant 28/2023, Arthritis UK grant 22467 Background Chronic low back pain (cLBP) is the leading cause of global disability, yet its pathophysiology remains elusive. While gut microbiome dysbiosis is implicated in pain via immune and neuroendocrine pathways, large-scale metagenomic evidence in cLBP is lacking. We investigated whether cLBP is associated with distinct stool microbial signatures. Methods We analysed stool shotgun metagenomic data from TwinsUK participants (300 cLBP, defined as pain persisting ≥3 months; 585 controls). All models adjusted for age, sex, BMI, smoking, sequencing batch, and twin-pair relatedness. Alpha diversity (Shannon, richness) was analysed using linear mixed-effects models; beta diversity (Aitchison, Bray-Curtis) was tested using PERMANOVA; and differential species abundance was assessed via generalized linear mixed-effects models. Sensitivity analyses adjusted for Healthy Eating Index (HEI), and proton pump inhibitor (PPI) use, with replication in the independent PredictUK cohort. Results Participants with cLBP exhibited significantly reduced Shannon diversity (β= −0.158, p= 0.031) and species richness (β= −0.177, p= 0.015). Seventeen bacterial species were differentially abundant at FDR <0.05 (10 enriched, 7 depleted in cLBP). Dietary quality did not differ between groups (p= 0.89), and all taxa remained robust after HEI adjustment. Seven taxa persisted after PPI adjustment, with attenuated species suggesting partial medication confounding. Beta diversity was not significantly associated with cLBP status. Conclusion cLBP is associated with reduced gut microbial diversity and a distinct taxonomic profile, independent of diet and medication use. These findings implicate gut microbiome dysbiosis as a potential contributor to cLBP pathophysiology and highlight specific microbial taxa as candidate targets for future mechanistic and therapeutic investigation.