Microbiome-gut-brain dysfunction in prodromal and symptomatic Lewy body diseases.
Microbiome-gut-brain dysfunction in prodromal and symptomatic Lewy body diseases.
复制标题
前驱期和症状性路易体疾病中的微生物组-肠-脑功能障碍。
DOI：
10.1007/s00415-022-11461-9
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发表时间：
2023-03
影响因子：
6
通讯作者：
Lin, Henry C.
中科院分区：
文献类型：
--
作者：
Ryman, Sephira;Vakhtin, Andrei A.;Richardson, Sarah Pirio;Lin, Henry C.
关键词：
路易体疾病，如帕金森病和伴路易体痴呆，其临床表型各不相同，但具有相同的决定性病理特征：α-突触核蛋白聚集。微生物群-肠-脑功能障碍可能在疾病过程的开始或进展中发挥作用，尽管存在多种潜在机制。我们讨论了评估路易体疾病的胃肠道发病机制的必要性，因为疾病机制可能跨越诊断类别，“身体优先”的临床综合征可能更好地解释各种疾病临床表现的异质性。我们讨论了两种主要假设，即α-突触核蛋白聚集发生在肠道并以朊病毒样方式扩散到大脑，或者由胃肠道功能障碍驱动的全身性炎症过程有助于路易体疾病的病理生理。这两种假设都假设生态失调和肠道通透性是关键机制和潜在的治疗靶点。最终，这项工作可以在明显的运动和认知症状发展之前确定针对初始疾病致病过程的早期干预措施。
Lewy body diseases, such as Parkinson’s disease and dementia with Lewy bodies, vary in their clinical phenotype but exhibit the same defining pathological feature, α-synuclein aggregation. Microbiome–gut–brain dysfunction may play a role in the initiation or progression of disease processes, though there are multiple potential mechanisms. We discuss the need to evaluate gastrointestinal mechanisms of pathogenesis across Lewy body diseases, as disease mechanisms likely span across diagnostic categories and a ‘body first’ clinical syndrome may better account for the heterogeneity of clinical presentations across the disorders. We discuss two primary hypotheses that suggest that either α-synuclein aggregation occurs in the gut and spreads in a prion-like fashion to the brain or systemic inflammatory processes driven by gastrointestinal dysfunction contribute to the pathophysiology of Lewy body diseases. Both of these hypotheses posit that dysbiosis and intestinal permeability are key mechanisms and potential treatment targets. Ultimately, this work can identify early interventions targeting initial disease pathogenic processes before the development of overt motor and cognitive symptoms.
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影响因子：
64.8
作者：
Arumugam, Manimozhiyan;Raes, Jeroen;Pelletier, Eric;Le Paslier, Denis;Yamada, Takuji;Mende, Daniel R.;Fernandes, Gabriel R.;Tap, Julien;Bruls, Thomas;Batto, Jean-Michel;Bertalan, Marcelo;Borruel, Natalia;Casellas, Francesc;Fernandez, Leyden;Gautier, Laurent;Hansen, Torben;Hattori, Masahira;Hayashi, Tetsuya;Kleerebezem, Michiel;Kurokawa, Ken;Leclerc, Marion;Levenez, Florence;Manichanh, Chaysavanh;Nielsen, H. Bjorn;Nielsen, Trine;Pons, Nicolas;Poulain, Julie;Qin, Junjie;Sicheritz-Ponten, Thomas;Tims, Sebastian;Torrents, David;Ugarte, Edgardo;Zoetendal, Erwin G.;Wang, Jun;Guarner, Francisco;Pedersen, Oluf;de Vos, Willem M.;Brunak, Soren;Dore, Joel;Weissenbach, Jean;Ehrlich, S. Dusko;Bork, Peer
通讯作者：
Bork, Peer
影响因子：
5
作者：
Bhattacharyya, Dipita;Mohite, Ganesh M.;Bhunia, Anirban
通讯作者：
Bhunia, Anirban
影响因子：
11.2
作者：
Brooks, DJ
通讯作者：
Brooks, DJ
影响因子：
15.1
作者：
Aho VTE;Houser MC;Pereira PAB;Chang J;Rudi K;Paulin L;Hertzberg V;Auvinen P;Tansey MG;Scheperjans F
通讯作者：
Scheperjans F
影响因子：
15.9
作者：
Bohorquez, Diego V.;Shahid, Rafiq A.;Liddle, Rodger A.
通讯作者：
Liddle, Rodger A.