Parkinson's disease (PD) is intricately linked to abnormal gut microbiota, yet the specific microbiota influencing clinical outcomes remain poorly understood. Our study identified a deficiency in the microbiota genus Blautia and a reduction in fecal short-chain fatty acid (SCFA) butyrate level in PD patients compared to healthy controls. The abundance of Blautia correlated with the clinical severity of PD. Supplementation with butyrate-producing bacterium B. producta demonstrated neuroprotective effects, attenuating neuroinflammation and dopaminergic neuronal death in mice, consequently ameliorating motor dysfunction. A pivotal inflammatory signaling pathway, the RAS-related pathway, modulated by butyrate, emerged as a key mechanism inhibiting microglial activation in PD. The change of RAS-NF-κB pathway in PD patients was observed. Furthermore, B. producta-derived butyrate demonstrated the inhibition of microglial activation in PD through regulation of the RAS-NF-κB pathway. These findings elucidate the causal relationship between specific gut microbiota and PD, presenting a novel microbiota-based treatment perspective for PD.

帕金森病 (PD) 与肠道微生物群异常密切相关，但影响临床结果的特定微生物群仍知之甚少。我们的研究发现，与健康对照组相比，帕金森病患者的肠道菌群存在缺陷，且粪便短链脂肪酸 (SCFA) 丁酸盐水平降低。Blautia的丰度与 PD 的临床严重程度相关。补充产生丁酸的细菌B.producta具有神经保护作用，可减轻小鼠的神经炎症和多巴胺能神经元死亡，从而改善运动功能障碍。关键的炎症信号通路，即由丁酸盐调节的 RAS 相关通路，成为抑制 PD 中小胶质细胞激活的关键机制。观察PD患者RAS-NF-κB通路的变化。此外，B.producta衍生的丁酸盐通过调节 RAS-NF-κB 通路抑制 PD 中的小胶质细胞活化。这些发现阐明了特定肠道微生物群与帕金森病之间的因果关系，为帕金森病提出了一种新的基于微生物群的治疗观点。