Analysis of Fecal Microbiota in Patients with Hypertension Complicated with Ischemic Stroke

J Mol Neurosci. 2023 Oct;73(9-10):787-803. doi: 10.1007/s12031-023-02149-4. Epub 2023 Sep 26.

Abstract

Ischemic stroke is a disease with a very high incidence in the clinic, and hypertension is the most important variable risk factor of ischemic stroke. Studies have shown that intestinal microbes are involved in the occurrence and development of various diseases. This study aims to explore whether intestinal microbes play an important role in the pathogenesis of ischemic stroke in a hypertensive population. In this study, the inpatients in the Department of Neurology and Cardiology of the Second Affiliated Hospital of Shandong First Medical University in April 2021 were selected, including seven patients with hypertension complicated with ischemic stroke and only seven patients with hypertension. After collecting the stool samples of patients, the gene sequence of the samples was detected by 16S rRNA sequencing technology, and the double-ended 2 × 150 bp sequencing was carried out. After sequencing, the results were analyzed by diversity analysis, species difference analysis, species function difference analysis, and other bioinformatics tests. According to the test results, serum proteomics and biochemical blood tests were carried out to verify. There was no significant difference in α diversity and β diversity between hypertension complicated with the cerebral infarction and hypertension groups. LEfSe analysis showed that at the genus level, compared with the hypertension group, Bacteroides, UCG_009, and Eisenbergiella had significantly increased relative abundance. The genera with relatively significantly reduced abundance are Ruminococcus_gnavus_group, Sutterellaceae, Burkholderia, and Prevotella and the LDA score of Prevotella is < - 4, which indicates that there are significant differences. Compared with the blood biochemical indexes, the results showed that the level of APOA1 in hypertensive patients with ischemic stroke was significantly higher than that in hypertensive patients (p < 0.05), but there was no significant difference in total cholesterol (CHOL), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein B (APOB), and free fatty acid (NEFA). Proteomic analysis showed that there were 89 up-regulated genes and 51 down-regulated genes in the serum of the two groups, and the expression of APOC2 and APOC3 in the cerebral infarction group with hypertension was significantly higher than that in the hypertension group (p < 0.05). The intestinal diversity of patients with hypertension complicated with stroke is similar to that of patients with hypertension, but there are differences in microbiota, among which Prevotella is the most significant. Prevotella could affect lipid metabolism so that APOC2 and APOC3 in the blood are significantly increased, leading to cerebral artery atherosclerosis and, finally, ischemic stroke. This provides a new idea for preventing and treating ischemic stroke in patients with hypertension, but the mechanism of Prevotella acting on apolipoprotein needs further verification by basic medical research.

Keywords: 16S rRNA; Intestinal microbiota; Ischemic stroke complicated with hypertension; Proteomic analysis.

MeSH terms

  • Apolipoprotein C-II
  • Cerebral Infarction
  • Humans
  • Hypertension* / complications
  • Ischemic Stroke* / complications
  • Microbiota*
  • Proteomics
  • RNA, Ribosomal, 16S
  • Stroke* / complications

Substances

  • RNA, Ribosomal, 16S
  • Apolipoprotein C-II