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寒冷环境通过调节肠道微生物群来调控缺血性中风。

Cold environment regulates ischemic stroke through modulation of gut microbiota.

作者信息

Zhou Xiao, Wei Chanjuan, Liu Jiaming, Xia Xiaoshuang, Wang Lin, Li Xin

机构信息

Department of Neurology, The Second Hospital of Tianjin Medical University, No. 23, Pingjiang Road, Tianjin, 300211, China.

Department of Geriatrics, The Second Hospital of Tianjin Medical University, Tianjin, China.

出版信息

Sci Rep. 2025 Jul 1;15(1):21558. doi: 10.1038/s41598-025-07614-1.

DOI:10.1038/s41598-025-07614-1
PMID:40593111
Abstract

Many diseases are influenced by environmental temperature, and recent studies have confirmed that cold exposure increases the risk of conditions such as ischemic stroke (IS). However, direct evidence supporting this hypothesis is lacking, and the molecular mechanisms through which cold exposure affects IS remain unclear. In this study, we found that chronic cold exposure increased platelet aggregation and the levels of certain inflammatory factors in high-risk stroke patients (HR), thereby increasing the risk of IS. Furthermore, before and after a cold wave, we observed gut microbiota dysbiosis in the HR group, including reduced relative abundance differences in Lachnospiraceae and Ruminococcaceae. The relative abundances of the Prevotella_9 and Catenibacterium genera increased, whereas that of Anaerostipes decreased. Notably, the results of fecal microbiota transplantation (FMT) indicated that cold-adapted microbiota transplantation partially replicated the microbiota characteristics of each donor subject and replicated the effects of cold exposure in C57BL/6J mice. Cold exposure impaired intestinal barrier function and interfered with microbial functions, such as increased lipid metabolism and LPS production, particularly by increasing the levels of TMAO derived from the gut microbiota. Our findings identify the significant role of abnormal gut microbiota-derived metabolites in cold exposure-related IS and highlight the potential opportunity to prevent or treat cold-related IS through the modulation of the gut microbiota.

摘要

许多疾病都受环境温度影响,近期研究证实,暴露于寒冷环境会增加缺血性中风(IS)等疾病的发病风险。然而,支持这一假说的直接证据尚缺,且寒冷暴露影响IS的分子机制仍不明晰。在本研究中,我们发现长期寒冷暴露会增加高危中风患者(HR)的血小板聚集及某些炎症因子水平,从而增加IS风险。此外,在寒潮前后,我们观察到HR组存在肠道微生物群失调,包括毛螺菌科和瘤胃球菌科的相对丰度差异减小。普雷沃菌属_9和链状杆菌属的相对丰度增加,而厌氧棒菌属的相对丰度降低。值得注意的是,粪便微生物群移植(FMT)结果表明,适应寒冷的微生物群移植部分重现了每个供体受试者的微生物群特征,并在C57BL/6J小鼠中重现了寒冷暴露的影响。寒冷暴露损害肠道屏障功能并干扰微生物功能,如增加脂质代谢和LPS产生,特别是通过增加源自肠道微生物群的氧化三甲胺(TMAO)水平。我们的研究结果确定了异常肠道微生物群衍生代谢物在寒冷暴露相关IS中的重要作用,并突出了通过调节肠道微生物群预防或治疗寒冷相关IS的潜在机会。

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本文引用的文献

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Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide and Ischemic Stroke.肠道微生物衍生代谢物三甲胺 N-氧化物与缺血性脑卒中。
Biomolecules. 2024 Nov 18;14(11):1463. doi: 10.3390/biom14111463.
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Mechanisms of time-restricted feeding-induced neuroprotection and neuronal plasticity in ischemic stroke as a function of circadian rhythm.限时进食诱导的缺血性中风神经保护和神经元可塑性的机制是昼夜节律的功能。
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在低温死亡的人心肌组织中过度表达;心脏死亡中与转录物和应激激素水平的关联。
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Global, regional, and national temporal trends in mortality and disability-adjusted life years for cardiovascular disease attributable to low temperature during 1990-2019: an age-period-cohort analysis of the global burden of disease 2019 study.全球、区域和国家归因于低温的心血管疾病死亡率和伤残调整生命年的时间趋势:2019 年全球疾病负担研究的年龄-时期-队列分析。
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KEGG: biological systems database as a model of the real world.京都基因与基因组百科全书(KEGG):作为现实世界模型的生物系统数据库。
Nucleic Acids Res. 2025 Jan 6;53(D1):D672-D677. doi: 10.1093/nar/gkae909.
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Effect of oral metformin on gut microbiota characteristics and metabolite fractions in normal-weight type 2 diabetic mellitus patients.口服二甲双胍对正常体重 2 型糖尿病患者肠道微生物特征和代谢物分数的影响。
Front Endocrinol (Lausanne). 2024 Aug 27;15:1397034. doi: 10.3389/fendo.2024.1397034. eCollection 2024.
7
Fucoidan ameliorates alcohol-induced liver injury in mice through Parabacteroides distasonis-mediated regulation of the gut-liver axis.岩藻聚糖硫酸酯通过拟杆菌属调控肠-肝轴改善小鼠的酒精性肝损伤。
Int J Biol Macromol. 2024 Nov;279(Pt 3):135309. doi: 10.1016/j.ijbiomac.2024.135309. Epub 2024 Sep 3.
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Human Gut Microbiota in Cardiovascular Disease.人体肠道微生物群与心血管疾病
Compr Physiol. 2024 Jun 27;14(3):5449-5490. doi: 10.1002/cphy.c230012.
9
Systemic Immune-Inflammation Index and Its Association with the Prevalence of Stroke in the United States Population: A Cross-Sectional Study Using the NHANES Database.全身免疫炎症指数及其与美国人群中风患病率的关联:一项使用美国国家健康与营养检查调查(NHANES)数据库的横断面研究
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10
PIM1-HDAC2 axis modulates intestinal homeostasis through epigenetic modification.PIM1-组蛋白去乙酰化酶2轴通过表观遗传修饰调节肠道稳态。
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