Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke
Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke
复制标题
肠道微生物群中的中风失调指数 (SDI) 与脑损伤和中风预后相关
DOI：
10.3389/fneur.2019.00397
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发表时间：
2019-04-24
影响因子：
3.4
通讯作者：
Yin, Jia
中科院分区：
文献类型：
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作者：
Xia, Geng-Hong;You, Chao;Yin, Jia
背景：卒中患者肠道微生物群存在显著的生态失调。将这些广泛而复杂的变化浓缩成一个指数将极大地促进肠道微生物组数据的临床应用。在此，我们根据急性缺血性卒中患者的肠道微生物群失调模式制定了肠道微生物群指数，并测试了该指数是否与脑损伤和早期预后相关。方法：共招募了104例急性缺血性卒中患者和90名健康个体，比较了他们的肠道微生物群，并建立了卒中生态失调指数（SDI）模型，该指数代表了卒中相关的生态失调模式。另外招募了83名患者和70名对照组进行验证。还评估了SDI与出院时脑卒中严重程度（美国国立卫生研究院卒中量表[NIHSS]评分）和预后（修正Rankin量表[mRS]评分：有利，0-2；不利，bb0 - 2）的关系。采用人类菌群相关（HFA）动物大脑中动脉闭塞（MCAO）模型，探讨肠道生态失调与脑卒中预后之间的因果关系。结果：18个属在脑卒中患者和健康人之间存在显著差异。SDI配方是根据这些微生物组差异设计的；脑卒中患者的SDI明显高于健康对照组。SDI单独区分脑卒中患者与对照组，训练组和验证组的auc分别为74.9%和84.3%。SDI与入院时NIHSS评分、出院时mRS评分呈显著正相关。Logistic回归分析显示，SDI是严重脑卒中（NIHSS≥8）和早期不良结局（mRS >2）的独立预测因子。与接受低sdi患者粪便移植的小鼠相比，接受高sdi患者粪便移植的小鼠出现了严重的脑损伤，肠道IL-17+ γδ T细胞升高（均P < 0.05）。结论：我们建立了一个指标来衡量脑卒中患者肠道菌群失调；在脑卒中小鼠模型中，该指标与患者预后显著相关，并与预后有因果关系。我们的模型促进了肠道微生物群数据在中风中的潜在临床应用，并增加了将肠道微生物群与中风联系起来的定量证据。
Background: Significant dysbiosis occurs in the gut microbiome of stroke patients. Condensing these broad, complex changes into one index would greatly facilitate the clinical usage of gut microbiome data. Here, we formulated a gut microbiota index in patients with acute ischemic stroke based on their gut microbiota dysbiosis patterns and tested whether the index was correlated with brain injury and early outcome. Methods: A total of 104 patients with acute ischemic stroke and 90 healthy individuals were recruited, and their gut microbiotas were compared and to model a Stroke Dysbiosis Index (SDI), which representing stroke-associated dysbiosis patterns overall. Another 83 patients and 70 controls were recruited for validation. The association of SDI with stroke severity (National Institutes of Health Stroke Scale [NIHSS] score) and outcome (modified Rankin scale [mRS] score: favorable, 0–2; unfavorable, >2) at discharge was also assessed. A middle cerebral artery occlusion (MCAO) model was used in human flora-associated (HFA) animals to explore the causal relationship between gut dysbiosis and stroke outcome. Results: Eighteen genera were significantly different between stroke patients and healthy individuals. The SDI formula was devised based on these microbiome differences; SDI was significantly higher in stroke patients than in healthy controls. SDI alone discriminated stroke patients from controls with AUCs of 74.9% in the training cohort and 84.3% in the validation cohort. SDI was significantly and positively correlated with NIHSS score on admission and mRS score at discharge. Logistic regression analysis showed that SDI was an independent predictor of severe stroke (NIHSS ≥8) and early unfavorable outcome (mRS >2). Mice receiving fecal transplants from high-SDI patients developed severe brain injury with elevated IL-17+ γδ T cells in gut compared to mice receiving transplants from low-SDI patients (all P < 0.05). Conclusions: We developed an index to measure gut microbiota dysbiosis in stroke patients; this index was significantly correlated with patients' outcome and was causally related to outcome in a mouse model of stroke. Our model facilitates the potential clinical application of gut microbiota data in stroke and adds quantitative evidence linking the gut microbiota to stroke.