Gut microbes impact stroke severity via the trimethylamine N-oxide pathway.
Gut microbes impact stroke severity via the trimethylamine N-oxide pathway.
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DOI：
10.1016/j.chom.2021.05.002
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发表时间：
2021-07-14
影响因子：
30.3
通讯作者：
Hazen SL
中科院分区：
文献类型：
--
作者：
Zhu W;Romano KA;Li L;Buffa JA;Sangwan N;Prakash P;Tittle AN;Li XS;Fu X;Androjna C;DiDonato AJ;Brinson K;Trapp BD;Fischbach MA;Rey FE;Hajjar AM;DiDonato JA;Hazen SL
临床研究表明，肠道微生物群衍生的代谢物三甲胺-N-氧化物（TMAO）的循环水平与中风风险之间存在相关性。然而，肠道微生物在中风中的因果作用尚未得到证实。在此，我们发现肠道微生物通过饮食中胆碱和TMAO的产生，直接影响脑梗死面积和中风后的不良结局。从低与高TMAO产生的人类受试者到无菌小鼠的粪便微生物移植表明，TMAO产生和中风严重程度都是可传播的特征。此外，采用多个小鼠中风模型和移植的定义的微生物群落与基因工程的人类胚胎到无菌小鼠，我们证明，微生物cutC基因（胆碱的TMA转化的酶源）是足以传输TMA/TMAO生产，提高脑梗死面积，并导致功能障碍。因此，我们揭示了肠道微生物群，特别是微生物TMAO途径，直接影响中风的严重程度。Zhu等人，通过肠道微生物移植研究证明，中风的严重程度是可以传播的。具体而言，发现代谢生物TMAO途径影响小鼠的中风大小和功能障碍。肠道微生物CutC增强宿主TMAO生成、脑梗死面积和卒中后功能缺陷。
Clinical studies demonstrate associations between circulating levels of the gut microbiota derived metabolite trimethylamine-N-oxide (TMAO) and incident stroke risks. However, a causal role of gut microbes in stroke has not yet been demonstrated. Herein we show that gut microbes, through dietary choline and TMAO generation, directly impact cerebral infarct size and adverse outcomes following stroke. Fecal microbial transplantation from low vs high TMAO producing human subjects into germ-free mice shows that both TMAO generation and stroke severity are transmissible traits. Further, employing multiple murine stroke models and transplantation of defined microbial communities with genetically engineered human commensals into germ-free mice, we demonstrate that the microbial cutC gene (an enzymatic source of choline to TMA transformation) is sufficient to transmit TMA/TMAO production, heighten cerebral infarct size and lead to functional impairment. We thus reveal that gut microbiota in general, and the metaorganismal TMAO pathway specifically, directly contributes to stroke severity. Zhu et al., demonstrate via gut microbial transplantation studies that stroke severity is transmissible. Specifically, the metaorganismal TMAO pathway was found to impact stroke size and functional impairment in mice. Gut microbial CutC enhanced host TMAO generation, cerebral infarct size, and post-stroke functional deficits.
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影响因子：
8.3
作者：
Jin Y;Barnett A;Zhang Y;Yu X;Luo Y
通讯作者：
Luo Y
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
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影响因子：
5.2
作者：
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Franklin CL
DOI：
10.1073/pnas.1215689109
发表时间：
2012-12-26
影响因子：
11.1
作者：
Craciun, Smaranda;Balskus, Emily P.
通讯作者：
Balskus, Emily P.
影响因子：
8.3
作者：
Fisher M;Feuerstein G;Howells DW;Hurn PD;Kent TA;Savitz SI;Lo EH;STAIR Group
通讯作者：
STAIR Group