Gut Microbiome Signatures Are Biomarkers for Cognitive Impairment in Patients With Ischemic Stroke.

Gut Microbiome Signatures Are Biomarkers for Cognitive Impairment in Patients With Ischemic Stroke.
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DOI:
10.3389/fnagi.2020.511562
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发表时间:
2020
影响因子:
4.8
通讯作者:
Sun J
Sun J
中科院分区:
医学2区
文献类型:
--
作者:
Ling Y;Gong T;Zhang J;Gu Q;Gao X;Weng X;Liu J;Sun J

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脑卒中后认知功能障碍(PSCI)是脑卒中后常见的神经精神并发症。越来越多的证据表明,肠道微生物群(GM)与神经精神疾病之间存在联系。我们先前的研究揭示了血管性痴呆小鼠模型中GM的变化。然而,PSCI的特征GM仍不清楚。本研究的目的是表征PSCI的GM,并探讨GM作为PSCI生物标志物的潜力。共有93例缺血性卒中患者入组本研究。根据卒中后3个月莫卡评分将患者分为两组。记录临床数据和生物学变量。用16S核糖体RNA测序分析GM组成,用线性判别分析效应大小(Lefse)鉴定特征GM。结果表明,与卒中后非认知功能障碍(PSNCI)组相比,PSCI组变形菌数量显著增加,在变形菌纲、目、科、属水平上也有相似的变化。经过年龄调整后,与PSNCI组相比,年龄匹配的PSCI组中厚壁菌门及其成员(包括梭菌属、梭菌目、毛螺菌科和毛螺菌科)的丰度显著降低。此外,GM与莫卡评分和PSCI的危险因素密切相关,包括较高的基线国立卫生研究院卒中量表评分、较高的同型半胱氨酸(Hcy)水平、较高的卒中复发率、脑白质疏松症和脑萎缩。KEGG结果显示PSCI患者的折叠、分选和降解模块(分子伴侣和折叠催化剂)丰富,辅因子和维生素、氨基酸和脂质代谢相关模块减少。经校正后,PSCI与肠杆菌科丰度之间存在显著相关性(P = 0.035)。此外,基于特征GM和肠杆菌科的受试者工作特征(ROC)模型可以区分PSCI患者和PSNCI患者[曲线下面积(AUC)分别为0.840,0.629]。我们的研究结果表明,特征GM,特别是肠杆菌科,可能有能力预测PSCI的中风后患者,这有望成为PSCI的临床生物标志物。
Post-stroke cognitive impairment (PSCI) is a common neuropsychiatric complication of stroke. Mounting evidence has demonstrated a connection between gut microbiota (GM) and neuropsychiatric disease. Our previous study revealed the changes in the GM in a mouse model of vascular dementia. However, the characteristic GM of PSCI remains unclear. This study aimed to characterize the GM of PSCI and explored the potential of GM as PSCI biomarkers. A total of 93 patients with ischemic stroke were enrolled in this study. The patients were divided into two groups according to their MoCA scores 3 months after stroke onset. Clinical data and biological variables were recorded. GM composition was analyzed using 16S ribosomal RNA sequencing, and the characteristic GM was identified by linear discriminant analysis Effect Size (Lefse). Our results showed that Proteobacteria was highly increased in the PSCI group compared with the post-stroke non-cognitive impairment (PSNCI) group, the similar alterations were also observed at the class, order, family, and genus levels of Proteobacteria. After age adjustments, the abundance of Firmicutes, and its members, including Clostridia, Clostridiales, Lachnospiraceae, and Lachnospiraceae_other, were significantly decreased in the age-matched PSCI group compared with the PSNCI group. Besides, the GM was closely associated with MoCA scores and the risk factors for PSCI, including higher baseline National Institute of Health Stroke Scale score, higher homocysteine (Hcy) level, higher prevalence of stroke recurrence, leukoaraiosis, and brain atrophy. The KEGG results showed the enriched module for folding, sorting and degradation (chaperones and folding catalysts) and the decreased modules related to metabolisms of cofactors and vitamins, amino acid, and lipid in PSCI patients. A significant correlation was observed between PSCI and the abundance of Enterobacteriaceae after adjustments (P = 0.035). Moreover, the receiver operating characteristic (ROC) models based on the characteristic GM and Enterobacteriaceae could distinguish PSCI patients from PSNCI patients [area under the curve (AUC) = 0.840, 0.629, respectively]. Our findings demonstrated that the characteristic GM, especially Enterobacteriaceae, might have the ability to predict PSCI in post-stroke patients, which are expected to be used as clinical biomarkers of PSCI.
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发表时间: 2018-01-15
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