Background: The causal relationship between childhood obesity and stroke remains unclear. Our objective was to elucidate the causal relationship between childhood obesity and the risk of stroke and its subtypes by performing Mendelian randomisation (MR) analyses.Methods: Genetic instruments for childhood obesity were obtained from a genome-wide association study (GWAS) of 13,848 European participants. Summary level data for stroke, intracerebral haemorrhage, ischaemic stroke (IS), and its subtypes were evaluated using the MEGASTROKE GWAS dataset, which included 446,696 European adults. Inverse-variance weighting, weighted-median analysis, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO), and MR-Robust Adjusted Profile Score were applied in this MR analysis. The leave-one-out sensitivity test, MR-PRESSO Global test, and Cochran’s Q test were conducted to confirm the accuracy and robustness of our results.Results: Genetic evaluations revealed that childhood obesity was associated with a higher risk of stroke (OR = 1.04, 95%CI: 1.01–1.07, p = 0.005) and IS (OR = 1.05, 95%CI: 1.02–1.08, p = 0.003), but not with intracerebral haemorrhage (ICH, OR = 0.93, 95%CI: 0.80–1.09, p = 0.39). In the subtype analysis, childhood obesity was also associated with large artery stroke (LAS, OR = 1.12, 95%CI: 1.02–1.22, p = 0.016) but not with cardioembolic stroke (OR = 1.06, 95%CI: 0.96–1.18, p = 0.21) and small vessel stroke (OR = 1.06, 95%CI: 0.98–1.15, p = 0.17). These results were stable in the sensitivity analysis and remained significant after Bonferroni correction.Conclusion: Our study provides evidence that childhood obesity is associated with a higher risk of stroke, IS, and LAS. The prevention of stroke, especially IS and LAS, should be promoted in populations with childhood obesity.

The high morbidity, mortality, and disability rates associated with cerebrovascular disease (CeVD) pose a severe danger to human health. Gut bacteria significantly affect the onset, progression, and prognosis of CeVD. Gut microbes play a critical role in gut-brain interactions, and the gut-brain axis is essential for communication in CeVD. The reflection of changes in the gut and brain caused by gut bacteria makes it possible to investigate early warning biomarkers and potential treatment targets. We primarily discussed the following three levels of brain-gut interactions in a systematic review of the connections between gut microbiota and several cerebrovascular conditions, including ischemic stroke, intracerebral hemorrhage, intracranial aneurysm, cerebral small vessel disease, and cerebral cavernous hemangioma. First, we studied the gut microbes in conjunction with CeVD and examined alterations in the core microbiota. This enabled us to identify the focus of gut microbes and determine the focus for CeVD prevention and treatment. Second, we discussed the pathological mechanisms underlying the involvement of gut microbes in CeVD occurrence and development, including immune-mediated inflammatory responses, variations in intestinal barrier function, and reciprocal effects of microbial metabolites. Finally, based on the aforementioned proven mechanisms, we assessed the effectiveness and potential applications of the current therapies, such as dietary intervention, fecal bacterial transplantation, traditional Chinese medicine, and antibiotic therapy.

BackgroundIntracerebral hemorrhage (ICH) is associated with high mortality and disability rates. This study aimed to investigate the relationship between sex, age, study year, risk factors, bleeding site, median year of study, and the incidence of ICH.MethodLiterature on the incidence of ICH published on 1 January 1980 and 1 January 2020, was systematically retrieved from PubMed and Embase databases. The random-effects model and subgroup analysis were used to explore the relationship between the incidence of ICH and different ages, sex, bleeding sites, and risk factors.ResultsWe summarized the epidemiological changes in ICH in the past 40 years according to 52 studies and found that the total incidence of ICH is 29.9 per 100,000 person-years (95% CI: 26.5–33.3), which has not decreased worldwide. The incidence of ICH in the Asian population is much higher than in other continents. In addition, the incidence of ICH increases with age and differs at the 85-year-old boundary. Men are more likely to develop ICH than women, and the basal ganglia region is the most common area for ICH. Of the 10 risk factors examined in this study, those with hypertension had the highest incidence of ICH, followed by those with excessive alcohol consumption and heart disease.ConclusionThe prevention and treatment of ICH still need to be improved continuously according to age, sex, risk factors, and other factors, and targeted and normative strategies should be gradually developed in the future.

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.

BackgroundThe relationship between the age at menarche (AAM) and the risk of intracerebral hemorrhage (ICH) and ischemic stroke (IS) is still up for debate. The purpose of this study was to investigate potential causal connections between them.MethodsGenome‐wide association analysis (GWAS) of AAM conducted by the MRC‐IEU consortium was utilized for association analyses of ICH and IS by two‐sample Mendelian randomization (MR) study. AAM data of the within‐family GWAS consortium were used as replication phase data to verify the causal relationship between each other. Inverse variance weighting (IVW) method was the primary method used in this MR study. For additional proof, the weighted median estimation, MR‐Egger regression, MR‐PRESSO test, and MR‐Robust Adjusted Profile Score evaluation were performed. The Cochran's Q test and the MR‐PRESSO global test were used, respectively, to examine the sensitivity and pleiotropy. Random effects meta‐analysis was utilized to analyze the causal data from the two consortiums to further explore the causality between AAM and ICH, IS.ResultsWe found that the AAM was causally linked with the risk of ICH (OR = 0.48, 95% CI: 0.28–0.80, p = 0.006). On the contrary, the causal effect from AAM to IS (OR = 0.98, 95% CI: 0.91–1.06, p = 0.64) has not been confirmed. For all subtypes of ICH, we found that nonlobar intracerebral hemorrhage (NLICH, OR = 0.41, 95% CI: 0.23–0.75, p = 0.004) but not lobar intracerebral hemorrhage (LICH, OR = 0.65, 95% CI: 0.34–1.24, p = 0.19) was associated with AAM without surprise. Similarly, we used the within‐family GWAS consortium data to explore causality and found that AAM may reduce the risk of ICH (OR = 0.78, 95% CI: 0.72–0.86, p = 9.5 × 10−8) and NLICH (OR = 0.68, 95% CI: 0.61–0.75, p = 3.4 × 10−13) by IVW methods, but is not related to IS (OR = 0.97, 95% CI: 0.93–1.02, p = 0.26). These findings are further supported by the meta‐analysis. Both Cochran's Q test and the MR‐PRESSO global test failed to detect the presence of sensitivity.ConclusionAAM and ICH, particularly NLICH, are causally related, but not LICH, IS, or its subtypes in European population.