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

Abstract

Intracerebral hemorrhage (ICH) is the most devastating subtype of stroke, but effective prevention and treatment strategies are lacking. Recently, gut microbiome and its metabolitesis are considered to be an influencing factor of stroke. However, little is known about the effects of the gut microbiome on ICH and host metabolic activity. Therefore, we used 16S sequencing, macrogenomics sequencing and untargeted metabolomics to explore the differences in gut microbial-metabolome interactions between patients with intracerebral hemorrhage and healthy control populations. We found a significant decrease in the phylum of Firmicutes and a significant increase of Bacteroidetes in ICH patients. At the genus level, Streptococcus, Bifidobacterium, Akkermansia, and Lactobacillus were more abundant in ICH patients. Macrogenomic analysis revealed active glycosaminoglycan degradation, heme synthesis, galactose degradation, lipopolysaccharide core region synthesis, and beta-Lactam resistance in ICH patients. Serum untargeted metabolomic analysis combined with ROC curves showed that octanoylcarnitine, decanoylcarnitine, dodecanoylcarnitine, glyceric acid, pyruvic acid, aspartic acid, methylcysteine, pyroglutamic acid, 9E-tetradecenoic acid, N-Acetylneuraminic acid, and aconitic acid were the best markers for the diagnosis of ICH. Correlation analysis showed that microbiome enriched in the gut of ICH patients were significantly correlated with serum metabolites, revealing a close correlation between the gut microbiome of ICH patients and the host metabolome, and significant differences from the healthy population. microbiota-host co-metabolites including pyruvic acid and 9E-tetradecenoic acid is associated with the the National Institutes of Health Stroke Scale (NIHSS) scores. In conclusion, microbiome-related metabolites in ICH patients was associated with the severity of ICH, the microbiota-host co-metabolites may be a potential may be potential therapeutic targets.

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

“…Over the last few decades, rapid advances in microbiome and metabolome studies have greatly aided our understanding of the pathogenic mechanisms underlying ICH ( Zhang et al, 2021b ; Chen et al, 2022 ). Most studies are animal or case–control studies, which can demonstrate an association with ICH but cannot establish a causal relationship.…”

“…Multi-omics research revealed a significant decrease in the phylum of Firmicutes and a significant increase in Bacteroidetes in ICH patients. 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.…”

“…The gut microbiota produces a wide variety of metabolites, as well as other blood metabolites, which have systemic effects on humans. The specific serum metabolites are also believed to affect neuroinflammation in patients with ICH ( Chen et al, 2022 ). ICH is characterized by the presence of bleeding within the brain parenchyma ( de Oliveira Manoel et al, 2016 ), with subsequent neuroinflammation caused by the byproducts of blood metabolism within the same parenchyma ( Alsbrook et al, 2023 ).…”

Causal association between 637 human metabolites and ovarian cancer: a mendelian randomization study

“…Our results also showed that octanoylcarnitine was negatively associated with OC. To date, the expression of octanoylcarnitine in different tumors remain conclusive [ 33 ], the expression in OC needs to be further verified. We also found that another acylcarnitine metabolite ( cis-4-decenyl carnitine ) was negatively correlated with OC.…”

The role of gut microbiota in cerebrovascular disease and related dementia

“…The study by Tan et al (2021), with a cohort of 40 acute ischaemic patients and 92 controls, showed that the intestinal microbiota was different in stroke patients compared with healthy controls, especially those with increased stroke severity, in which SCFA levels, especially acetate, were associated with an increased risk of 90-day poor functional outcomes. A recent clinical study also demonstrated that gut dysbiosis takes place after haemorrhagic stroke (Chen, Wang, et al, 2022): By using 16S RNA sequencing, macrogenomics sequencing and untargeted metabolomics to explore the differences in gut microbial-metabolome interactions between patients with intracerebral haemorrhage and healthy control populations, they found a significant decrease in the phylum of Firmicutes and a significant increase of Bacteroidetes in haemorrhagic stroke patients, which is accompanied by changes in serum microbial metabolites and correlates with the severity of intracerebral haemorrhage (Chen, Wang, et al, 2022). In addition, a role of GM in post-stroke prognosis and early stroke outcome has been demonstrated in a study including 104 patients with acute ischaemic stroke and 90 healthy individual showing that the stroke dysbiosis index (SDI) correlated not only with brain injury but also with early unfavourable outcome (Xia et al, 2019).…”