Abstract
Increasing evidence suggests that features of the gut microbiota correlate with ischemic stroke. However, the specific characteristics of the gut microbiota in patients suffering different types of ischemic stroke, or recovering from such strokes, have rarely been studied, and potential microbiotic predictors of different types of stroke have seldom been analyzed. We subjected fecal specimens from patients with lacunar or non-lacunar acute ischemic infarctions, and those recovering from such strokes, to bacterial 16S rRNA sequencing and compared the results to those of healthy volunteers. We identified microbial markers of different types of ischemic stroke and verified that these were of diagnostic utility. Patients with two types of ischemic stroke, and those recovering from ischemic stroke, exhibited significant shifts in microbiotic diversities compared to healthy subjects. Cluster of Orthologous Groups of Proteins (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed reduced metabolic and transport-related pathway activities in ischemic stroke patients. We performed fivefold cross-validation using a Random Forest model to identify two optimal bacterial species (operational taxonomic units; OTUs) serving as markers of lacunar infarction; these were Lachnospiraceae (OTU_45) and Bacteroides (OTU_4), and the areas under the receiver operating characteristic curves (AUCs under the ROCs) were 0.881 and 0.872 respectively. In terms of non-lacunar acute ischemic infarction detection, the two optimal species were Bilophila (OTU_330) and Lachnospiraceae (OTU_338); the AUCs under the ROCs were 0.985 and 0.929 respectively. In post-ischemic stroke patients, the three optimal species were Pseudomonas (OTU_35), Sphingomonadaceae (OTU_303), and Akkermansia (OTU_9); the AUCs under the ROCs were 1, 0.897, and 0.846 respectively. Notably, the gut microbial markers were of considerable value for utility when diagnosing lacunar infarction, non-lacunar acute ischemic infarction, and post-ischemic stroke. This study is the first to characterize the gut microbiotic profiles of patients with lacunar or non-lacunar, acute ischemic strokes, and those recovering from stroke, and to identify microbiotic predictors of such strokes.
Highlights
Ischemic stroke is a major cause of death and severe neurological disability; global post-stroke mortality is 39% (Wang et al, 2017)
Fecal samples were collected from 16 healthy volunteers (N group, n = 16); 20 patients with ischemic stroke: lacunar infarction (LI group, n = 10), non-lacunar acute ischemic infarction (AI group, n = 10); and 10 post-ischemic stroke patients who had undergone 15 days of treatment after acute ischemic stroke (PI group, n = 10)
The operational taxonomic units (OTUs) annotated for subsequent analyses included 22 phyla, 116 families, and 217 genera of gut microbes inferred via V4 amplicon sequences (39 to 297 base pairs); the among-sample similarity was 97% (Figure 1A)
Summary
Ischemic stroke is a major cause of death and severe neurological disability; global post-stroke mortality is 39% (Wang et al, 2017). Acute ischemic infarction is the most common type of stroke, associated with high rates of death and disability (Paciaroni et al, 2008). Postischemic stroke patients have experienced acute ischemic stroke and often deal with severe sequelae including cognitive and anxiodepressive disorders, fatigue, and restricted participation in daily life (Zhang et al, 2018). Though the progress were made in the treatments of stroke, the prognosis is poor, most ischemic stroke patients are diagnosed at advanced stages causing high risks of disability and mortality. Early diagnostic measures of ischemic stroke need to be explored so as to greatly improve the management of the disease
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