Gut Microbiome and Metabolome Changes in Chronic Low Back Pain Patients With Vertebral Bone Marrow Lesions

Abstract

Background

Chronic low back pain (LBP) is a significant global health concern, often linked to vertebral bone marrow lesions (BML), particularly fatty replacement (FR). This study aims to explore the relationship between the gut microbiome, serum metabolome, and FR in chronic LBP patients.

Methods

Serum metabolomic profiling and gut microbiome analysis were conducted in chronic LBP patients with and without FR (LBP + FR, n = 40; LBP, n = 40) and Healthy Controls (HC, n = 31). The study investigates alterations in branched-chain amino acids (BCAAs) levels and identifies key microbial species associated with BCAA metabolism. In vitro experiments elucidate the role of BCAAs in adipogenesis of bone marrow mesenchymal stem cells (BM-MSCs) via the SIRT4 pathway.

Results

Chronic LBP patients with FR exhibit depleted BCAA levels in their serum metabolome, along with alterations in the gut microbiome. Specific microbial species, including Ruminococcus gnavus, Roseburia hominis, and Lachnospiraceae bacterium 8 1 57FAA, are identified as influential in BCAA metabolism and BM-MSCs metabolism. In vitro experiments demonstrate the ability of BCAAs to induce BM-MSCs adipogenesis through SIRT4 pathway activation.

Conclusion

This study sheds light on the intricate relationship between the disturbed gut ecosystem, serum metabolites, and FR in chronic LBP. Dysbiosis in the gut microbiome may contribute to altered BCAA degradation, subsequently promoting BM-MSCs adipogenesis and FR. Understanding these interactions provides insights for targeted therapeutic strategies to mitigate chronic LBP associated with FR by restoring gut microbial balance and modulating serum metabolite profiles.