Li Wentian, Tu Ji, Zheng Jinjian, Das Abhirup, Yan Qi, Jiang Xiaotao, Ding Wenyuan, Bai Xupeng, Lai Kaitao, Yang Sidong, Yang Cao, Zou Jun, Diwan Ashish D, Zheng Zhaomin
Spine Labs, St. George and Sutherland Clinical School University of new South Wales Kogarah Australia.
Gulbali Institute, School of Agricultural, Environmental and Veterinary Sciences Charles Sturt University Wagga Wagga Australia.
JOR Spine. 2025 Jan 27;8(1):e70042. doi: 10.1002/jsp2.70042. eCollection 2025 Mar.
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.
Serum metabolomic profiling and gut microbiome analysis were conducted in chronic LBP patients with and without FR (LBP + FR, = 40; LBP, = 40) and Healthy Controls (HC, = 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.
Chronic LBP patients with FR exhibit depleted BCAA levels in their serum metabolome, along with alterations in the gut microbiome. Specific microbial species, including , , and , 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.
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.
慢性腰痛是一个重大的全球健康问题，常与椎体骨髓病变（BML）相关，尤其是脂肪替代（FR）。本研究旨在探讨慢性腰痛患者肠道微生物群、血清代谢组与FR之间的关系。
对有和没有FR的慢性腰痛患者（LBP + FR，n = 40；LBP，n = 40）以及健康对照（HC，n = 31）进行血清代谢组学分析和肠道微生物群分析。该研究调查支链氨基酸（BCAAs）水平的变化，并确定与BCAA代谢相关的关键微生物种类。体外实验阐明了BCAAs通过SIRT4途径在骨髓间充质干细胞（BM-MSCs）脂肪生成中的作用。
患有FR的慢性腰痛患者血清代谢组中BCAA水平降低，同时肠道微生物群也发生了变化。特定的微生物种类，包括[具体微生物名称1]、[具体微生物名称2]和[具体微生物名称3]，被确定对BCAA代谢和BM-MSCs代谢有影响。体外实验证明了BCAAs通过激活SIRT4途径诱导BM-MSCs脂肪生成的能力。
本研究揭示了慢性腰痛中肠道生态系统紊乱、血清代谢物与FR之间的复杂关系。肠道微生物群失调可能导致BCAA降解改变，进而促进BM-MSCs脂肪生成和FR。了解这些相互作用为通过恢复肠道微生物平衡和调节血清代谢物谱来减轻与FR相关的慢性腰痛的靶向治疗策略提供了见解。
