Niu Mengqi, Li Jing, Zhuang Xiaoman, Yangyang Chenkai, Chen Yali, Zhang Yingqian, Maes Michael
Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, China.
Mol Pain. 2025 Jan-Dec;21:17448069251332140. doi: 10.1177/17448069251332140. Epub 2025 Mar 21.
Fibromyalgia (FM) is a complex disorder characterized by chronic pain, fatigue, and functional impairments, with unclear pathological mechanisms. Gut microbiota and plasma metabolites have been implicated in FM, but their causal relationships remain unexplored. This study aims to assess the causal relationships between gut microbiota, plasma metabolites, and FM using Mendelian randomization (MR) analysis and to explore potential mediating mechanisms. Public genome-wide association study data were analyzed using bidirectional MR. Associations between gut microbiota, plasma metabolites, and FM were evaluated, and multivariable MR identified mediating metabolites. Results were validated with inverse variance weighted, MR-Egger, and weighted median methods, with metabolic pathway enrichment analysis for further insights. MR identified protective associations between FM and four taxa (family , genus , genus , and order ) and risk associations with genus and genus . Additionally, 82 plasma metabolites linked to pathways such as caffeine metabolism, α-linolenic acid metabolism, GLP-1, and incretin regulation were associated with FM. Mediation analysis revealed and influenced FM risk through 2,3-dihydroxypyridine and palmitoylcholine. Personalized dietary interventions, such as limiting caffeine intake, increasing omega-3 fatty acid consumption, adopting a low glycemic index diet, and reducing the intake of high-oxalate foods, may effectively alleviate FM-related symptoms by modulating metabolic pathways, reducing inflammation, and mitigating oxidative stress. This study highlights the intricate interactions between the gut microbiota and metabolic pathways, providing critical scientific evidence and actionable targets for clinical interventions, dietary management, and precision medicine approaches in FM treatment.
纤维肌痛（FM）是一种复杂的疾病，其特征为慢性疼痛、疲劳和功能障碍，病理机制尚不清楚。肠道微生物群和血浆代谢物与纤维肌痛有关，但其因果关系仍未得到探索。本研究旨在使用孟德尔随机化（MR）分析评估肠道微生物群、血浆代谢物与纤维肌痛之间的因果关系，并探索潜在的中介机制。使用双向MR分析公开的全基因组关联研究数据。评估肠道微生物群、血浆代谢物与纤维肌痛之间的关联，并通过多变量MR确定中介代谢物。结果用逆方差加权、MR-Egger和加权中位数方法进行验证，并进行代谢途径富集分析以获得进一步的见解。MR确定了纤维肌痛与四个分类群（科 、属 、属 和目 ）之间的保护性关联以及与属 和属 的风险关联。此外，82种与咖啡因代谢、α-亚麻酸代谢、胰高血糖素样肽-1和肠促胰岛素调节等途径相关的血浆代谢物与纤维肌痛有关。中介分析显示 和 通过2,3-二羟基吡啶和棕榈酰胆碱影响纤维肌痛风险。个性化饮食干预，如限制咖啡因摄入、增加ω-3脂肪酸摄入、采用低血糖指数饮食和减少高草酸盐食物的摄入，可能通过调节代谢途径、减轻炎症和缓解氧化应激来有效缓解纤维肌痛相关症状。本研究强调了肠道微生物群与代谢途径之间的复杂相互作用，为纤维肌痛治疗中的临床干预、饮食管理和精准医学方法提供了关键的科学证据和可操作的靶点。
