A pilot study: Gut microbiota, metabolism and inflammation in hypertensive intracerebral haemorrhage

Abstract

Aims: In recent years, the incidence rate of hypertensive intracerebral haemorrhage (HICH) has been increasing, accompanied by high mortality and morbidity, which has brought a heavy burden to the social economy. However, the pathogenesis of HICH is still unclear. This study intends to explore the mechanism of gut microbiota metabolism and inflammation in the process of HICH to provide a theoretical basis for the diagnosis and treatment of HICH.Methods and Results: HE staining showed that the brain tissues of model group had obvious oedema injury, which indicated that the HICH model was successfully constructed. ELISA analysis showed that IL-1β and TNF-α levels in blood and brain tissues were significantly increased, and IL-10 level was significantly decreased in blood. IHC analysis showed that microglia and macrophages were activated in the model group. 16S rRNA sequence showed that the diversity of gut microbiota in HICH patients decreased. Also, the microbiota belonging to Firmicutes, Proteobacteria and Verrucomicrobia changed significantly. LC-MS/MS analysis showed that the metabolic phenotype of HICH patients changed. Also, the 3,7-dimethyluric acid-and 7-methylxanthine-related metabolic pathways of caffeine metabolism pathways were downregulated in patients with HICH. Bacteroides was negatively correlated with the IL-1β and TNF-α levels. Blautia was negatively correlated with the IL-1β and TNF-α levels, and positively correlated with the IL-10 level. Akkermansia was negatively correlated with the 3,7-dimethyluric acid and 7-methylxanthine. Conclusion:Our study suggested that HICH was accompanied by the increased inflammation marker levels in peripheral blood and brain, decreased gut microbiota diversity, altered gut metabolic phenotype and downregulation of caffeine metabolism pathway. Significance and Impact of the Study:Our study reported that HICH accompanied by the increased inflammation, decreased gut microbiota diversity and altered gut metabolic phenotype. Due to the number of patients, this work was a pilot study.

Multi-omics reveals specific host metabolism-microbiome associations in intracerebral hemorrhage

“…Akkermansia muciniphila is the most important species in Verrucomicrobiota, and were more significant enrichment in ICH. Two recent studies that included 10 patients each with parenchymal hemorrhage reported a significant increase in abundance of Verrucomicrobiota (Li et al, 2022;Xiong et al, 2022), which is consistent with our results. This bacteria uses mucin O-glycan, a major component of intestinal mucus, as the main carbon source and is sialidase-rich species, while excessive degradation of mucin by microbiome can exacerbate intestinal inflammation (Patel et al, 2022;Yao et al, 2022).…”

Genetically predicted causality between gut microbiota, blood metabolites, and intracerebral hemorrhage: a bidirectional Mendelian randomization study

“…At the genus level, Streptococcus, Lactobacillus, Bifidobacterium, and Akkermansia were found to be abundant in ICH patients ( Chen et al, 2022 ). Moreover, Li et al (2022b) and Xiong et al (2022) reported that the abundance of Akkermansia in patients with parenchymal hemorrhage was significantly increased. Several animal model studies consistently indicated that ICH is characterized by a significant increase in Actinomycetes, Bacteroidetes, and Firmicutes, with minor changes in other bacterial populations ( Yu et al, 2021a ; Zhang et al, 2021a ).…”

The role of gut microorganisms and metabolites in intracerebral hemorrhagic stroke: a comprehensive review

“…According to recent research, ICH has been found to be associated with alterations in the composition of the gut microbiota. Li W. et al (2022) demonstrated significant changes in the abundance of Firmicutes , Proteobacteria , and Verrucomicrobia in the gut microbiota following the occurrence of ICH, as compared to a healthy gut microbiota. At the taxonomic level of genus, a notable decrease in the abundance of Bacteroides, Blautia, Faecalibacterium, Subdoligranulum, Bifidobacterium, Agathobacter , and Romboutsia was observed, whereas a significant increase in the abundance of Escherichia-Shigella , Akkermansia , Lactobacillus , and Lachnoclostridium was evident.…”