Gut microbiota is causally associated with poststroke cognitive impairment through lipopolysaccharide and butyrate.
Gut microbiota is causally associated with poststroke cognitive impairment through lipopolysaccharide and butyrate.
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肠道微生物群通过脂多糖和丁酸盐与中风后认知障碍存在因果关系
DOI：
10.1186/s12974-022-02435-9
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发表时间：
2022-04-04
影响因子：
9.3
通讯作者：
Yin J
中科院分区：
文献类型：
--
作者：
Wang H;Zhang M;Li J;Liang J;Yang M;Xia G;Ren Y;Zhou H;Wu Q;He Y;Yin J
脑卒中后认知障碍（PSCI）在脑卒中患者中普遍存在。PSCI的病因在很大程度上仍然未知。我们之前发现中风会引起肠道菌群失调，从而影响脑损伤。因此，我们旨在研究肠道微生物群是否与PSCI的发病机制有关。选取脑卒中患者83例，在脑卒中发病3个月后采用蒙特利尔认知评估（MoCA）评分对其认知功能进行测量。分析患者外周血炎症因子水平和肠道菌群组成。将患者的粪便微生物群移植给中风小鼠，以检验肠道微生物群与PSCI之间的因果关系。Morris水迷宫实验评价小鼠认知功能。脑卒中患者分为PSCI和非PSCI分别为34例和49例。与非PSCI患者相比，PSCI患者的肠道肠杆菌科、脂多糖（LPS）和外周炎症标志物水平显著升高。同样，接受PSCI患者微生物群的中风小鼠（PSCI小鼠）比接受nPSCI患者微生物群的小鼠（nPSCI小鼠）表现出更高水平的肠杆菌科、肠道toll样受体-4 （TLR4）表达、循环LPS、LPS结合蛋白（LBP）和炎症因子，以及更低水平的粪便丁酸盐，更严重的肠道破坏和认知障碍。此外，我们观察到与nPSCI小鼠相比，PSCI小鼠血脑屏障（BBB）完整性、小胶质细胞激活、海马CA1区神经元凋亡和丘脑Aβ沉积的恶化。脑卒中后腹腔注射LPS引起的病理与PSCI小鼠相似。通过饮用水补充丁酸钠（NaB）可挽救PSCI小鼠的这些有害变化。我们的数据首次表明肠道微生物群与PSCI之间存在因果关系，这可能是由包括LPS和丁酸盐在内的炎症调节代谢物介导的。在线版本包含补充材料，可在10.1186/s12974-022-02435-9获得。
Poststroke cognitive impairment (PSCI) is prevalent in stroke patients. The etiology of PSCI remains largely unknown. We previously found that stroke induces gut microbiota dysbiosis which affects brain injury. Hereby, we aimed to investigate whether the gut microbiota contributes to the pathogenesis of PSCI. 83 stroke patients were recruited and their cognitive function were measured by Montreal Cognitive Assessment (MoCA) scores 3 months after stroke onset. The peripheral inflammatory factor levels and gut microbiota compositions of the patients were analyzed. Fecal microbiota transplantation from patients to stroke mice was performed to examine the causal relationship between the gut microbiota and PSCI. The cognitive function of mice was evaluated by Morris water maze test. 34 and 49 stroke patients were classified as PSCI and non-PSCI, respectively. Compared with non-PSCI patients, PSCI patients showed significantly higher levels of gut Enterobacteriaceae, lipopolysaccharide (LPS) and peripheral inflammation markers. Consistently, stroke mice that received microbiota from PSCI patients (PSCI mice) presented a higher level of Enterobacteriaceae, intestinal Toll-like receptor-4 (TLR4) expression, circulating LPS, LPS-binding protein (LBP) and inflammatory cytokines, and a lower level of fecal butyrate, severer intestine destruction and cognitive impairment than mice that received microbiota from nPSCI patients (nPSCI mice). In addition, we observed exacerbations in blood–brain barrier (BBB) integrity, microglial activation, neuronal apoptosis in the CA1 region of the hippocampus, and Aβ deposition in the thalamus of PSCI mice in comparison with nPSCI mice. Intraperitoneal injection of LPS after stroke caused similar pathology to those seen in PSCI mice. Supplementation with sodium butyrate (NaB) via drinking water rescued these detrimental changes in PSCI mice. Our data indicate a cause–effect relationship between gut microbiota and PSCI for the first time, which is likely mediated by inflammation-regulating metabolites including LPS and butyrate. The online version contains supplementary material available at 10.1186/s12974-022-02435-9.
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影响因子：
82.9
作者：
Benakis C;Brea D;Caballero S;Faraco G;Moore J;Murphy M;Sita G;Racchumi G;Ling L;Pamer EG;Iadecola C;Anrather J
通讯作者：
Anrather J
中风后痴呆 - 全面回顾。
影响因子：
9.3
作者：
Mijajlović MD;Pavlović A;Brainin M;Heiss WD;Quinn TJ;Ihle-Hansen HB;Hermann DM;Assayag EB;Richard E;Thiel A;Kliper E;Shin YI;Kim YH;Choi S;Jung S;Lee YB;Sinanović O;Levine DA;Schlesinger I;Mead G;Milošević V;Leys D;Hagberg G;Ursin MH;Teuschl Y;Prokopenko S;Mozheyko E;Bezdenezhnykh A;Matz K;Aleksić V;Muresanu D;Korczyn AD;Bornstein NM
通讯作者：
Bornstein NM
DOI：
10.1126/science.aam9949
发表时间：
2017-08-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Byndloss MX;Olsan EE;Rivera-Chávez F;Tiffany CR;Cevallos SA;Lokken KL;Torres TP;Byndloss AJ;Faber F;Gao Y;Litvak Y;Lopez CA;Xu G;Napoli E;Giulivi C;Tsolis RM;Revzin A;Lebrilla CB;Bäumler AJ
通讯作者：
Bäumler AJ
影响因子：
4
作者：
Ling, Yi;Gu, Qilu;Sun, Jing
通讯作者：
Sun, Jing
影响因子：
4.8
作者：
Ling Y;Gong T;Zhang J;Gu Q;Gao X;Weng X;Liu J;Sun J
通讯作者：
Sun J