ORIGINAL RESEARCH article
Front. Med.
Sec. Translational Medicine
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1636860
Identification of novel gut microbiota-related microbes-related biomarkers in cerebral hemorrhagic stroke
Provisionally accepted
- The First hospital of Hebei Medical University, Shijiazhuang, China
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Hemorrhagic stroke is the most lethal type of stroke and poses a serious threat to global human health. The immune response after hemorrhagic stroke is characterized by the release of pro-inflammatory cytokines, the mobilization of immune cells and the dysregulation of the gut microbiota. The dysregulation of the gut microbiota also affects the prognosis and inflammatory response of patients. In this study, we explored the gut microbiota biomarkers related to cerebral hemorrhagic stroke through bioinformatics analysis and experimental verification. The differentially expressed genes (DEGs) in intracerebral hemorrhage (ICH) were analyzed using the GSE24265 dataset, and the gut microbiota-relatedmicrobes-related genes (GMRGs) were obtained from GeneCards database and previous literature. We obtained 806 DEGs and 686 GMRGs, and selected 65 common genes as gut microbiota-relatedmicrobes-related DEGs (GMRDEGs) for further analysis. Functional enrichment analysis revealed that these GMRDEGs were associated with leukocyte cell-cell adhesion, migration, and immune response modulation, and enriched in immune related diseases and tumor necrosis factor (TNF) and interleukin-17 (IL-17) signaling pathways. Moreover, machine learning algorithms were applied to screen the characteristic genes from GMRDEGs.Finally, four hub genes were selected, namely lymphoid enhancer-binding factor 1 (LEF1), integrin subunit alpha X (ITGAX), biliverdin IXbeta reductase (BLVRB), and activating transcription factor 4 (ATF4). These four GMRDEGs were significantly upregulated in ICH patients and were significantly correlated with the degree of immune cell infiltration. Furthermore, we validated the upregulation of these four genes in the plasma samples from ICH patients. In the mouse model of ICH, we demonstrated that fecal microbiota transplantation (FMT) significantly attenuated the symptoms of ICH in mice, restored the decreased levels of tight junction proteins in the colon of mice, and increased the levels of four hub genes in the cerebral hematoma of mice. In 2 conclusion, LEF1, ITGAX, BLVRB, ATF4 are four gut microbiota-relatedmicrobesrelated biomarkers in ICH, which may be involved in the brain-gut axis in ICH.
Keywords: cerebral hemorrhagic stroke, Gut microbe, Bioinformatics analysis, Hub genes, fecal microbiota transplantation
Received: 28 May 2025; Accepted: 07 Aug 2025.
Copyright: © 2025 Ye, Li, Li and Mu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiue Mu, The First hospital of Hebei Medical University, Shijiazhuang, China
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