A multi-omics bidirectional mendelian randomization study and meta-analysis on the causal relationship between gut microbiota, inflammatory proteins, and fibromyalgia.
Mengqi Niu, Jing Li, Victoria Sarafian, Michael Maes
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引用次数: 0
Abstract
Background: Fibromyalgia (FM) is a chronic disorder characterized by widespread pain and immune dysregulation. Emerging evidence suggests that gut microbiota and inflammatory proteins may contribute to the development of FM.
Objective: The aim of this study was to investigate the causal relationships between gut microbiota, inflammatory proteins (cytokines/chemokines), and FM using bidirectional Mendelian randomization (MR) and meta-analysis approaches.
Methods: MR analyses were conducted using genetic data from European populations, employing methods such as MR-IVW, MR-Egger, and MR-weighted median. Reverse MR was also performed, with FM treated as the exposure. A meta-analysis was conducted to consolidate the findings.
Results: Ruminococcus gauvreauii was identified as a risk factor for FM, while Enterorhabdus, Parabacteroides, Butyricicoccus, and Prevotella 9 were found to be protective. Five inflammatory proteins C-X-C motif chemokine 5 (CXCL5), S100-A12, Leukemia inhibitory factor receptor (LIFR), Monocyte chemoattractant protein 2 (MCP-2/CCL8), and Tumor necrosis factor (TNF-α) exhibited protective associations, while Natural killer cell receptor 2B4 (NKCR-2B4/CD244) and Interleukin-12 subunit beta (IL-12β) were associated with an increased risk of FM.
Conclusion: This study highlights the role of gut microbiota and inflammatory proteins (cytokines/chemokines) in the pathogenesis of FM. Through Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, the findings suggest their involvement in immune regulation, inflammatory responses, and viral pathways. These findings provide new insights into potential therapeutic targets for modulating gut health and immune responses, opening new avenues for future research and clinical interventions.
背景:纤维肌痛(FM)是一种以广泛性疼痛和免疫调节失调为特征的慢性疾病。新出现的证据表明,肠道微生物群和炎性蛋白可能会导致 FM 的发生:本研究旨在利用双向孟德尔随机化(MR)和荟萃分析方法研究肠道微生物群、炎症蛋白(细胞因子/趋化因子)和 FM 之间的因果关系:采用 MR-IVW、MR-Egger 和 MR 加权中位数等方法,利用欧洲人群的遗传数据进行 MR 分析。此外,还进行了反向 MR 分析,将 FM 视为暴露。为了巩固研究结果,还进行了荟萃分析:结果:高乌头反刍球菌(Ruminococcus gauvreauii)被确定为 FM 的危险因素,而肠杆菌(Enterorhabdus)、副乳杆菌(Parabacteroides)、丁酸球菌(Butyricicoccus)和前驱菌 9(Prevotella 9)则具有保护作用。五种炎症蛋白C-X-C motif趋化因子5(CXCL5)、S100-A12、白血病抑制因子受体(LIFR)、单核细胞趋化蛋白2(MCP-2/CCL8)和肿瘤坏死因子(TNF-α)具有保护作用,而自然杀伤细胞受体2B4(NKCR-2B4/CD244)和白细胞介素-12亚基β(IL-12β)则与FM风险增加有关:本研究强调了肠道微生物群和炎症蛋白(细胞因子/趋化因子)在 FM 发病机制中的作用。通过基因本体(GO)功能富集和京都基因和基因组百科全书(KEGG)通路分析,研究结果表明它们参与了免疫调节、炎症反应和病毒通路。这些发现为调节肠道健康和免疫反应的潜在治疗靶点提供了新的见解,为未来的研究和临床干预开辟了新的途径。