Exploring the associations of gut microbiota with inflammatory and the early hematoma expansion in intracerebral hemorrhage: From variations to potential therapeutic targets

Abstract

Background Alterations in the intestinal flora composition can influence host inflammation, metabolism, and immune response. Although a great deal of research has explored the possibility of a systemic inflammatory response and dysbiosis of the gut microbiota after an intracerebral hemorrhage (ICH), the relationships between gut microbiota and blood inflammatory parameters as well as their role in the hematoma expansion following an early-stage mild-to-moderate ICH (emICH) remain unknown. In addition to examining microbiological indicators and underlying treatment targets, this study analyzes these changes and associations in order to predict and prevent hematoma expansion after emICH. Methods A total of 100 participants were enrolled, comprising 70 emICH patients (30 with hematoma expansion and 40 with non-hematoma expansion, i.e., HE and NE groups) and 30 age- and sex-matched healthy controls (HC). Utilizing 16S rRNA gene amplicon sequencing, we examined the gut microbiota community in the HE group and investigated its associations with blood inflammatory parameters. Results Our results revealed significantly reduced microbial ecosystem richness and evenness in the HE group compared to the HC and NE groups. Substantial changes in the structure of the gut microbiota were seen in the emICH group, particularly in HE. These changes included a rise in the number of gram-negative pro-inflammatory bacteria and a decline in the level of probiotic bacteria. We also identified significant positive correlations between HE-enriched bacteria and systemic inflammatory levels. Several microbial biomarkers (such as Escherichia_Shigella, Enterobacter, and Porphyromonas) were revealed in differentiating HE from HC and NE. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis unveiled dysregulations in fundamental physiological pathways, particularly inflammatory response (such as Toll-like receptor signaling pathway), within the HE group. Conclusions Our findings suggest that emICH patients, particularly those with HE, exhibit distinct host-microbe interactions in comparison to healthy controls. We deduced that emICH could rapidly trigger the dysbiosis of intestinal flora, and the disturbed microbiota could, in turn, exacerbate inflammatory response and increase the risk of hematoma expansion. Our comprehensive findings, indicate the potential of intestinal flora as a predictive tool, emphasizing its significance as a preventive target for HE.