肠道微生物群紊乱与急性轻型缺血性卒中患者不良功能预后的相关性研究

doi:10.3969/j.issn.1673-5765.2024.12.004

摘要/Abstract

摘要： 目的通过建立急性轻型缺血性卒中（mild ischemic stroke，MIS）患者队列，探索肠道微生物群与MIS患者临床功能预后间的关系，寻找不良功能预后的干预靶点。
方法前瞻性连续纳入2018年9月—2023年3月于南方医科大学南方医院神经内科住院的卒中事件后7 d内入院的急性MIS（入院NIHSS评分≤5分）患者，根据90 d随访评估结果，分为预后良好（mRS评分≤2分）组及预后不良（mRS评分＞2分）组。入院后24 h内收集入组患者粪便样本，通过16S核糖体RNA高通量测序对肠道微生物群进行检测。分析临床特点和肠道微生物相关指标对MIS患者预后不良的影响，并建立基于肠道微生物的MIS患者不良功能预后发生风险的临床预测模型。
结果预后不良组与预后良好组MIS患者肠道微生物群组成存在显著差异（P=0.001）。在菌群组成上，线性判别分析效应大小（linear discriminant analysis effect size，LEfSe）分析发现大肠埃希菌志贺菌属（Escherichia Shigella）是预后不良组患者的优势菌属，预后良好组患者厚壁菌门（Firmicutes）、梭菌纲（Clostridia）丰度明显富集。相关性分析发现，大肠埃希菌志贺菌属丰度与中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值、系统性免疫炎症指数呈显著正相关。多因素logistic回归分析发现，校正后厚壁菌门（OR 0.587，95%CI 0.351～0.980，P=0.042）、梭菌纲（OR 0.577，95%CI 0.341～0.977，P=0.041）丰度升高是不良功能预后的保护因素，大肠埃希菌志贺菌属（OR 2.483，95%CI 1.370～4.500，P=0.003）丰度增加是不良功能预后的独立危险因素。将厚壁菌门、梭菌纲、大肠埃希菌志贺菌属分别与临床指标结合建立不良功能预后预测模型，AUC分别为0.842（95%CI 0.756～0.928）、0.840（95%CI 0.752～0.928）、0.863（95%CI 0.787～0.939）。
结论厚壁菌门、梭菌纲及大肠埃希菌志贺菌属丰度可能是MIS患者临床功能预后相关的潜在生物标志物。

文章导读： 本研究通过建立观察性、单中心、前瞻性的急性轻型缺血性卒中患者队列，利用微生物组学检测，分析发现厚壁菌门、梭菌纲及大肠埃希菌志贺菌属丰度可能是患者临床功能预后相关的潜在生物标志物。

关键词: 肠道微生物; 急性轻型缺血性卒中; 预后; 生物标志物

Abstract: Objective To investigate the relationship between gut microbiota and clinical prognosis in acute mild ischemic stroke (MIS) patients by establishing a cohort of patients with MIS, and to identify intervention targets for poor functional prognosis.
Methods Patients with acute MIS (NIHSS score≤5 points) were prospectively and continuously enrolled in this study. These patients were admitted to the Department of Neurology at Nanfang Hospital, Southern Medical University between September 2018 and March 2023, within 7 days of the onset of the stroke events. According to the results of a 90-day follow-up, the patients were divided into the good prognosis (mRS score≤2 points) group and the poor prognosis (mRS score >2 points) group. Stool samples were collected from all patients within 24 hours of admission, and the gut microbiota composition was analyzed using 16S ribosomal RNA high-throughput sequencing. The effects of clinical characteristics and gut microbiota-related indicators on the poor prognosis of MIS patients were analyzed. Additionally, clinical prediction models were established to assess the risk of poor prognosis of MIS patients based on gut microbiota.
Results There were significant differences in the composition of gut microbiota between MIS patients with poor and good prognoses (P=0.001). In terms of the gut microbiota composition, linear discriminant analysis effect size revealed that Escherichia Shigella was the dominant genera in patients with poor prognosis, while the abundance of Firmicutes and Clostridia were significantly enriched in patients with good prognosis. Further correlation analysis showed that the abundance of Escherichia Shigella was positively correlated with the neutrophil-to-lymphocyte ratio, the platelet-to-lymphocyte ratio, and the systemic immune-inflammation index. Multivariate logistic regression analysis showed that the increased abundance of Firmicutes (OR 0.587, 95%CI 0.351-0.980, P=0.042) and Clostridia (OR 0.577, 95%CI 0.341-0.977, P=0.041) after adjustment was a protective factor for poor functional prognosis, whereas the increased abundance of Escherichia Shigella (OR 2.483, 95%CI 1.370-4.500, P=0.003) was an independent risk factor for poor functional prognosis. By combining the Firmicutes, Clostridia, and Escherichia Shigella with clinical indicators, predictive models for poor functional prognosis were established, with AUC values of 0.842 (95%CI 0.756-0.928), 0.840 (95%CI 0.752-0.928), and 0.863 (95%CI 0.787-0.939), respectively.
Conclusions The abundance of Firmicutes, Clostridia, and Escherichia Shigella may serve as potential biomarkers for predicting the clinical functional prognosis of MIS patients.

Key words: Gut microbiota; Acute mild ischemic stroke; Prognosis; Biomarker

中图分类号:

任悦冉, 梁京儒, 郑逸锋, 尹恝. 肠道微生物群紊乱与急性轻型缺血性卒中患者不良功能预后的相关性研究[J]. 中国卒中杂志, 2024, 19(12): 1383-1391.

REN Yueran, LIANG Jingru, ZHENG Yifeng, YIN Jia. Correlation between Gut Microbiota Dysbiosis and Poor Functional Prognosis in Patients with Acute Mild Ischemic Stroke[J]. Chinese Journal of Stroke, 2024, 19(12): 1383-1391.

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