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Zhou Zhang,1,2,* Xin Li,1,* Wen Tang,1 Hao Xie,1 Hong-Jiang Wang,1 Hao-Yu Xie,1,3 Chu-Huai Wang1 1Department of Rehabilitation Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510275, People’s Republic of China; 2Guangdong Provincial Clinical Research Center for Rehabilitation Medicine, Guangzhou, 510275, People’s Republic of China; 3Department of Rehabilitation Medicine, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chu-Huai Wang, Email wangchuh@mail.sysu.edu.cn Hao-Yu Xie, Email xiehy55@mail.sysu.edu.cnBackground: Chronic nonspecific low back pain (cNLBP) represents the most prevalent musculoskeletal disorder encountered in clinical practice, constituting approximately two-thirds of all chronic low back pain cases. Epidemiological studies have identified significant gender differences in the incidence of cNLBP, with women exhibiting a slightly higher prevalence and reporting greater pain severity compared to men. However, the underlying mechanisms contributing to the increased severity of cNLBP in women remain largely unexplored. Our research is the first to explore fatty acid biomarkers in female patients with cNLBP undergoing physiotherapy from the perspectives of metabolomics and lipidomics.Methods: The study comprised 13 healthy female volunteers and 15 women diagnosed with cNLBP. Metabolomic and lipidomic analyses were employed to identify lipid metabolites closely associated with cNLBP in women. Subsequently, the 15 patients with cNLBP underwent manual therapy and exercise therapy, which incorporated both manual therapy and exercise therapy. Each therapy session lasted 50 minutes and was conducted over six sessions, occurring every two days. The Visual Analog Scale (VAS) scores of the patients were evaluated before and after treatment, and serum samples were collected for lipid determination at both pre- and post-treatment intervals.Results: Our metabolomic and lipidomic analyses revealed significantly elevated levels of three fatty acids (FAs): C14:0 FA (P=0.046), C20:0 FA (P=0.000001), and C20:1 FA (P=0.0007)), alongside significantly reduced levels of C20:5 (P=0.021) FA in women with cNLBP compared to healthy female volunteers. Receiver Operating Characteristic (ROC) curve analyses demonstrated that the Area Under the Curve (AUC) for these FAs exceeded 75%, indicating robust diagnostic performance. Notably, C20:0 FA exhibited an AUC greater than 95%, suggesting its potential as the most effective biomarker for diagnosing female patients with cNLBP. Additionally, physiotherapy significantly reduced pain levels in these women and was associated with a substantial decrease in blood FA levels.Conclusion: The study revealed a significant correlation between FA levels and female patients with cNLBP undergoing physiotherapy, thereby providing valuable insights for the development of personalized treatment approaches.Trial Registration: (Chinese Clinical Trial Registry (https://www.chictr.org.cn), No.ChiCTR2300076620, 10/13/2023).Keywords: fatty acid, metabolome, lipidome, chronic nonspecific low back pain |