Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism
Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism
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DOI：
10.1016/j.cell.2020.02.035
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发表时间：
2020-03-19
期刊：
影响因子：
64.5
通讯作者：
Haghikia, Aiden
中科院分区：
文献类型：
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作者：
Duscha, Alexander;Gisevius, Barbara;Haghikia, Aiden
短链脂肪酸由肠道细菌从不可消化的膳食纤维中加工产生，具有免疫调节特性。在此，我们研究丙酸（PA）在多发性硬化症（MS）这种自身免疫性和神经退行性疾病中的作用。与对照组相比，多发性硬化症患者的血清和粪便中丙酸含量显著降低，尤其是在首次复发之后。在一项概念验证研究中，我们给未接受过治疗的多发性硬化症患者补充丙酸，并将其作为多发性硬化症免疫疗法的补充。在摄入丙酸2周后，我们观察到具有功能活性的调节性T细胞（Treg）显著且持续增加，而Th1和Th17细胞显著减少。事后分析显示，摄入丙酸3年后，年复发率降低，残疾情况稳定，脑萎缩减轻。功能性微生物组分析显示，摄入丙酸后肠道中诱导Treg细胞的基因表达增加。此外，丙酸使多发性硬化症中Treg细胞的线粒体功能和形态正常化。我们的研究结果表明，丙酸可作为多发性硬化症药物的一种有效的免疫调节补充剂。
Short-chain fatty acids are processed from indigestible dietary fibers by gut bacteria and have immunomodulatory properties. Here, we investigate propionic acid (PA) in multiple sclerosis (MS), an autoimmune and neurodegenerative disease. Serum and feces of subjects with MS exhibited significantly reduced PA amounts compared with controls, particularly after the first relapse. In a proof-of-concept study, we supplemented PA to therapy-naive MS patients and as an add-on to MS immunotherapy. After 2 weeks of PA intake, we observed a significant and sustained increase of functionally competent regulatory T (Treg) cells, whereas Th1 and Th17 cells decreased significantly. Post-hoc analyses revealed a reduced annual relapse rate, disability stabilization, and reduced brain atrophy after 3 years of PA intake. Functional microbiome analysis revealed increased expression of Treg-cell-inducing genes in the intestine after PA intake. Furthermore, PA normalized Treg cell mitochondria! function and morphology in MS. Our findings suggest that PA can serve as a potent immunomodulatory supplement to MS drugs.