Rifaximin Modifies Gut Microbiota and Attenuates Inflammation in Parkinson's Disease: Preclinical and Clinical Studies.
Rifaximin Modifies Gut Microbiota and Attenuates Inflammation in Parkinson's Disease: Preclinical and Clinical Studies.
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帕金森病 (PD) 患者表现出独特的肠道微生物群，这可能会促进肠道源性炎症。利福昔明是一种不可吸收的抗生素，可以改变肠道微生物群。本研究调查了利福昔明对帕金森病患者肠道微生物群和炎症状态的影响。该研究检验了长期利福昔明治疗对体内转基因PD小鼠（MitoPark）和短期利福昔明治疗对PD患者的影响。利福昔明治疗引起转基因 PD 小鼠肠道微生物群的显着变化；特别是，它降低了 Prevotellaceae UCG-001 的相对丰度，增加了 Bacteroides、Muribaculum 和 Lachnospiraceae UCG-001 的相对丰度。利福昔明治疗可减弱血清白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α、claudin-5和occludin，这表明全身炎症减少并保护血脑屏障完整性。利福昔明治疗的 MitoPark 小鼠比对照小鼠表现出更好的运动和记忆性能，小胶质细胞激活较低，海马神经元存活率增加。在PD患者中，7天的利福昔明治疗导致治疗6个月后Flavonifractor的相对丰度增加，血浆促炎细胞因子水平的变化与基线血浆白细胞介素1α水平呈负相关。总之，本研究证明利福昔明通过调节肠道微生物群对转基因 PD 小鼠发挥神经保护作用。我们观察到基线炎症较高的患者可能受益于利福昔明治疗。考虑到利福昔明的耐受性和安全性，随机对照试验应研究长期治疗对特定 PD 患者的疾病缓解效果。
Patients with Parkinson’s disease (PD) exhibit distinct gut microbiota, which may promote gut-derived inflammation. Rifaximin is a nonabsorbable antibiotic that can modify gut microbiota. The present study investigated the effect of rifaximin on gut microbiota and inflammation status in PD. The study examined the effect of long-term rifaximin treatment on in vivo transgenic PD mice (MitoPark) and short-term rifaximin treatment on patients with PD. Rifaximin treatment caused a significant change in gut microbiota in the transgenic PD mice; in particular, it reduced the relative abundance of Prevotellaceae UCG-001 and increased the relative abundance of Bacteroides, Muribaculum, and Lachnospiraceae UCG-001. Rifaximin treatment attenuated serum interleukin-1β, interleukin-6 and tumor necrosis factor-α, claudin-5 and occludin, which indicated the reduction of systemic inflammation and the protection of the blood–brain barrier integrity. The rifaximin-treated MitoPark mice exhibited better motor and memory performance than did the control mice, with lower microglial activation and increased neuronal survival in the hippocampus. In the patients with PD, 7-day rifaximin treatment caused an increase in the relative abundance of Flavonifractor 6 months after treatment, and the change in plasma proinflammatory cytokine levels was negatively associated with the baseline plasma interleukin-1α level. In conclusion, the present study demonstrated that rifaximin exerted a neuroprotective effect on the transgenic PD mice by modulating gut microbiota. We observed that patients with higher baseline inflammation possibly benefited from rifaximin treatment. With consideration for the tolerability and safety of rifaximin, randomized controlled trials should investigate the disease-modification effect of long-term treatment on select patients with PD.
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影响因子：
3.7
作者：
Bajaj JS;Heuman DM;Sanyal AJ;Hylemon PB;Sterling RK;Stravitz RT;Fuchs M;Ridlon JM;Daita K;Monteith P;Noble NA;White MB;Fisher A;Sikaroodi M;Rangwala H;Gillevet PM
通讯作者：
Gillevet PM
影响因子：
7.3
作者：
Kinashi Y;Hase K
通讯作者：
Hase K
影响因子：
6
作者：
Chan L;Chung CC;Chen JH;Yu RC;Hong CT
通讯作者：
Hong CT
DOI：
10.4061/2011/436813
发表时间：
2011-02-22
期刊：
Parkinson's disease
影响因子：
--
作者：
Ferrari CC;Tarelli R
通讯作者：
Tarelli R
DOI：
10.1002/hep.31708
发表时间：
2021-09
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Caraceni P;Vargas V;Solà E;Alessandria C;de Wit K;Trebicka J;Angeli P;Mookerjee RP;Durand F;Pose E;Krag A;Bajaj JS;Beuers U;Ginès P;Liverhope Consortium
通讯作者：
Liverhope Consortium