Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease.
Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease.
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DOI：
10.1016/j.cell.2016.11.018
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发表时间：
2016-12-01
期刊：
影响因子：
64.5
通讯作者：
Mazmanian SK
中科院分区：
文献类型：
--
作者：
Sampson TR;Debelius JW;Thron T;Janssen S;Shastri GG;Ilhan ZE;Challis C;Schretter CE;Rocha S;Gradinaru V;Chesselet MF;Keshavarzian A;Shannon KM;Krajmalnik-Brown R;Wittung-Stafshede P;Knight R;Mazmanian SK
肠道微生物群影响神经发育，调节行为，并导致神经系统疾病。然而，肠道细菌与神经退行性疾病之间的功能性联系仍未被探索。突触核蛋白病的特征是α - 突触核蛋白（αSyn）的聚集，通常导致运动功能障碍，帕金森病（PD）就是一个例子。我们利用过表达αSyn的小鼠在此报告，肠道微生物群是运动缺陷、小胶质细胞激活和αSyn病理所必需的。抗生素治疗可改善，而微生物重新定殖会促进成年动物的病理生理，这表明肠道和大脑之间的出生后信号传导调节疾病。事实上，给无菌小鼠口服特定的微生物代谢产物会促进神经炎症和运动症状。值得注意的是，与来自健康人类捐赠者的微生物群移植相比，用帕金森病患者的微生物群定殖αSyn过表达小鼠会加剧身体损伤。这些发现表明肠道细菌调节小鼠的运动障碍，并提示人类微生物组的改变是帕金森病的一个风险因素。
在帕金森病模型中，肠道微生物的信号对于神经炎症反应以及标志性的胃肠和α - 突触核蛋白依赖性运动缺陷是必需的。
The intestinal microbiota influence neurodevelopment, modulate behavior, and contribute to neurological disorders. However, a functional link between gut bacteria and neurodegenerative diseases remains unexplored. Synucleinopathies are characterized by aggregation of the protein α-synuclein (αSyn), often resulting in motor dysfunction as exemplified by Parkinson's disease (PD). Using mice that overexpress αSyn, we report herein that gut microbiota are required for motor deficits, microglia activation, and αSyn pathology. Antibiotic treatment ameliorates, while microbial re-colonization promotes, pathophysiology in adult animals, suggesting postnatal signaling between the gut and the brain modulates disease. Indeed, oral administration of specific microbial metabolites to germ-free mice promotes neuroinflammation and motor symptoms. Remarkably, colonization of αSyn-overexpressing mice with microbiota from PD patients enhances physical impairments compared to microbiota transplants from healthy human donors. These findings reveal that gut bacteria regulate movement disorders in mice, and suggest that alterations in the human microbiome represent a risk factor for PD. Signals from gut microbes are required for the neuroinflammatory responses as well as hallmark gastrointestinal and α-synuclein-dependent motor deficits in a model of Parkinson's disease.
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影响因子：
3.7
作者：
Hasegawa S;Goto S;Tsuji H;Okuno T;Asahara T;Nomoto K;Shibata A;Fujisawa Y;Minato T;Okamoto A;Ohno K;Hirayama M
通讯作者：
Hirayama M
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5.3
作者：
Fleming, SM;Salcedo, J;Chesselet, MF
通讯作者：
Chesselet, MF
影响因子：
5.4
作者：
Gilbert JA;Jansson JK;Knight R
通讯作者：
Knight R
影响因子：
11
作者：
Clarke, G.;Grenham, S.;Cryan, J. F.
通讯作者：
Cryan, J. F.
帕金森病病理从大鼠胃肠道传播到大脑的直接证据
影响因子：
12.7
作者：
Holmqvist, Staffan;Chutna, Oldriska;Li, Jia-Yi
通讯作者：
Li, Jia-Yi