Minerbi Amir, Gonzalez Emmanuel, Brereton Nicholas, Fitzcharles Mary-Ann, Chevalier Stéphanie, Shir Yoram
Alan Edwards Pain Management Unit, McGill University Health Centre, Montreal, QC, Canada.
Institute for Pain Medicine, Rambam Health Campus, Haifa, Israel.
Pain. 2023 Feb 1;164(2):e66-e76. doi: 10.1097/j.pain.0000000000002694. Epub 2022 May 19.
Alterations in the composition and function of the gut microbiome in women with fibromyalgia have recently been demonstrated, including changes in the relative abundance of certain bile acid-metabolizing bacteria. Bile acids can affect multiple physiological processes, including visceral pain, but have yet to be explored for association to the fibromyalgia gut microbiome. In this study, 16S rRNA sequencing and targeted metabolomic approaches were used to characterize the gut microbiome and circulating bile acids in a cohort of 42 women with fibromyalgia and 42 healthy controls. Alterations in the relative abundance of several bacterial species known to metabolize bile acids were observed in women with fibromyalgia, accompanied by significant alterations in the serum concentration of secondary bile acids, including a marked depletion of α-muricholic acid. Statistical learning algorithms could accurately detect individuals with fibromyalgia using the concentration of these serum bile acids. Serum α-muricholic acid was highly correlated with symptom severity, including pain intensity and fatigue. Taken together, these findings suggest serum bile acid alterations are implicated in nociplastic pain. The changes observed in the composition of the gut microbiota and the concentration of circulating secondary bile acids seem congruent with the phenotype of increased nociception and are quantitatively correlated with symptom severity. This is a first demonstration of circulating bile acid alteration in individuals with fibromyalgia, potentially secondary to upstream gut microbiome alterations. If corroborated in independent studies, these observations may allow for the development of molecular diagnostic aids for fibromyalgia as well as mechanistic insights into the syndrome.
最近已证实纤维肌痛女性的肠道微生物群组成和功能发生了改变,包括某些胆汁酸代谢细菌相对丰度的变化。胆汁酸可影响多种生理过程,包括内脏疼痛,但尚未探讨其与纤维肌痛肠道微生物群的关联。在本研究中,采用16S rRNA测序和靶向代谢组学方法,对42名纤维肌痛女性和42名健康对照者的肠道微生物群和循环胆汁酸进行了表征。在纤维肌痛女性中观察到几种已知可代谢胆汁酸的细菌物种相对丰度的改变,同时伴随着次级胆汁酸血清浓度的显著改变,包括α-鼠胆酸的明显减少。统计学习算法可以使用这些血清胆汁酸的浓度准确检测出纤维肌痛患者。血清α-鼠胆酸与症状严重程度高度相关,包括疼痛强度和疲劳。综上所述,这些发现表明血清胆汁酸改变与伤害感受性疼痛有关。肠道微生物群组成和循环次级胆汁酸浓度的变化似乎与伤害感受增加的表型一致,并且在数量上与症状严重程度相关。这首次证明了纤维肌痛患者循环胆汁酸的改变,可能继发于上游肠道微生物群的改变。如果在独立研究中得到证实,这些观察结果可能有助于开发纤维肌痛的分子诊断辅助工具,并深入了解该综合征的发病机制。
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