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 mitochondrial function and morphology in MS. Our findings suggest that PA can serve as a potent immunomodulatory supplement to MS drugs.

短链脂肪酸由肠道细菌从不可消化的膳食纤维加工而成，具有免疫调节特性。在这里，我们研究了丙酸 (PA) 在多发性硬化症 (MS)（一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 PA 含量显着降低，尤其是在第一次复发后。在一项概念验证研究中，我们向未接受过治疗的多发性硬化症患者补充 PA，并将其作为多发性硬化症免疫治疗的补充。摄入 PA 两周后，我们观察到功能性调节性 T (Treg) 细胞显着且持续增加，而 Th1 和 Th17 细胞显着减少。事后分析显示，服用 PA 三年后，年复发率降低，残疾稳定，脑萎缩减少。功能性微生物组分析显示，摄入 PA 后肠道中 Treg 细胞诱导基因的表达增加。此外，PA 使 MS 中的 Treg 细胞线粒体功能和形态正常化。我们的研究结果表明，PA 可以作为多发性硬化症药物的有效免疫调节补充剂。