Dataset Information

Gut Microbiome Signatures Are Biomarkers for Cognitive Impairment in Patients With Ischemic Stroke.

ABSTRACT: Post-stroke cognitive impairment (PSCI) is a common neuropsychiatric complication of stroke. Mounting evidence has demonstrated a connection between gut microbiota (GM) and neuropsychiatric disease. Our previous study revealed the changes in the GM in a mouse model of vascular dementia. However, the characteristic GM of PSCI remains unclear. This study aimed to characterize the GM of PSCI and explored the potential of GM as PSCI biomarkers. A total of 93 patients with ischemic stroke were enrolled in this study. The patients were divided into two groups according to their MoCA scores 3 months after stroke onset. Clinical data and biological variables were recorded. GM composition was analyzed using 16S ribosomal RNA sequencing, and the characteristic GM was identified by linear discriminant analysis Effect Size (Lefse). Our results showed that Proteobacteria was highly increased in the PSCI group compared with the post-stroke non-cognitive impairment (PSNCI) group, the similar alterations were also observed at the class, order, family, and genus levels of Proteobacteria. After age adjustments, the abundance of Firmicutes, and its members, including Clostridia, Clostridiales, Lachnospiraceae, and Lachnospiraceae_other, were significantly decreased in the age-matched PSCI group compared with the PSNCI group. Besides, the GM was closely associated with MoCA scores and the risk factors for PSCI, including higher baseline National Institute of Health Stroke Scale score, higher homocysteine (Hcy) level, higher prevalence of stroke recurrence, leukoaraiosis, and brain atrophy. The KEGG results showed the enriched module for folding, sorting and degradation (chaperones and folding catalysts) and the decreased modules related to metabolisms of cofactors and vitamins, amino acid, and lipid in PSCI patients. A significant correlation was observed between PSCI and the abundance of Enterobacteriaceae after adjustments (P = 0.035). Moreover, the receiver operating characteristic (ROC) models based on the characteristic GM and Enterobacteriaceae could distinguish PSCI patients from PSNCI patients [area under the curve (AUC) = 0.840, 0.629, respectively]. Our findings demonstrated that the characteristic GM, especially Enterobacteriaceae, might have the ability to predict PSCI in post-stroke patients, which are expected to be used as clinical biomarkers of PSCI.

SUBMITTER: Ling Y

PROVIDER: S-EPMC7645221 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Gut Microbiome Signatures Are Biomarkers for Cognitive Impairment in Patients With Ischemic Stroke.

Ling Yi Y Gong Tianyu T Zhang Junmei J Gu Qilu Q Gao Xinxin X Weng Xiongpeng X Liu Jiaming J Sun Jing J

Frontiers in aging neuroscience 20201023

Post-stroke cognitive impairment (PSCI) is a common neuropsychiatric complication of stroke. Mounting evidence has demonstrated a connection between gut microbiota (GM) and neuropsychiatric disease. Our previous study revealed the changes in the GM in a mouse model of vascular dementia. However, the characteristic GM of PSCI remains unclear. This study aimed to characterize the GM of PSCI and explored the potential of GM as PSCI biomarkers. A total of 93 patients with ischemic stroke were enroll ...[more]

PMID: 33192448

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Project description:BackgroundPoststroke cognitive impairment is a severe and common clinical complication that constitutes a substantial global health burden. We aimed to evaluate the association of 3 cardiac biomarkers in combination with poststroke cognitive impairment and their prognostic significance.Methods and resultsThis prospective study included 566 patients with ischemic stroke. Cardiac biomarkers, including sST2 (soluble suppression of tumorigenicity-2 receptor), GDF-15 (growth differentiation factor-15), and NT-proBNP (N-terminal pro-B-type natriuretic peptide), were measured. Cognitive impairment was defined as a Mini-Mental State Examination score of <27 or a Montreal Cognitive Assessment score of <25 at 3 months after ischemic stroke. Odds of cognitive impairment 3 months after ischemic stroke increased with the number of elevated cardiac biomarkers (sST2, GDF-15, and NT-proBNP; Ptrend<0.001). The multivariable adjusted odds ratios (95% CIs) of cognitive impairment defined by the Mini-Mental State Examination and Montreal Cognitive Assessment were 2.45 (1.48-4.07) and 1.86 (1.10-3.14) for the participants with ≥2 elevated cardiac biomarkers, respectively, compared with those without any elevated cardiac biomarker. Additionally, higher cardiac biomarker scores were associated with an increased risk of cognitive impairment (Ptrend<0.05). Simultaneously adding all 3 cardiac biomarkers to the basic model with traditional risk factors significantly improved the risk prediction of Mini-Mental State Examination-defined cognitive impairment (net reclassification improvement=34.99%, P<0.001; integrated discrimination index=2.67%, P<0.001). Similar findings were observed using the Montreal Cognitive Assessment scores.ConclusionsAn increased number of elevated novel cardiac biomarkers were associated with an increased odds of poststroke cognitive impairment, suggesting that a combination of these cardiac biomarkers may improve the risk prediction of cognitive impairment.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

Project description:BackgroundIntegrative analysis approaches of metagenomics and metabolomics have been widely developed to understand the association between disease and the gut microbiome. However, the different profiling patterns of different metabolic samples in the association analysis make it a matter of concern which type of sample is the most closely associated with gut microbes and disease. To address this lack of knowledge, we investigated the association between the gut microbiome and metabolomic profiles of stool, urine, and plasma samples from ischemic stroke patients and healthy subjects.MethodsWe performed metagenomic sequencing (feces) and untargeted metabolomics analysis (feces, plasma, and urine) from ischemic stroke patients and healthy volunteers. Differential analyses were conducted to find key differential microbiota and metabolites for ischemic stroke. Meanwhile, Spearman's rank correlation and linear regression analyses were used to study the association between microbiota and metabolites of different metabolic mixtures.ResultsUntargeted metabolomics analysis shows that feces had the most abundant features and identified metabolites, followed by urine and plasma. Feces had the highest number of differential metabolites between ischemic stroke patients and the healthy group. Based on the association analysis between metagenomics and metabolomics of fecal, urine, and plasma, fecal metabolome showed the strongest association with the gut microbiome. There are 1073, 191, and 81 statistically significant pairs (P < 0.05) in the correlation analysis for fecal, urine, and plasma metabolome. Fecal metabolites explained the variance of alpha-diversity of the gut microbiome up to 31.1%, while urine and plasma metabolites only explained the variance of alpha-diversity up to 13.5% and 10.6%. Meanwhile, there were more significant differential metabolites in feces than urine and plasma associated with the stroke marker bacteria.ConclusionsThe systematic association analysis between gut microbiome and metabolomics reveals that fecal metabolites show the strongest association with the gut microbiome, followed by urine and plasma. The findings would promote the association study between the gut microbiome and fecal metabolome to explore key factors that are associated with diseases. We also provide a user-friendly web server and a R package to facilitate researchers to conduct the association analysis of gut microbiome and metabolomics.

Project description:Background and Aims: Systemic inflammation is associated with an increased risk of cognitive impairment and dementia, but the associations between them in stroke patients are less clear. We examined the impact of systemic inflammation represented as the neutrophil-lymphocyte ratio (NLR) on the development of post-stroke cognitive impairment (PSCI) and domain-specific cognitive outcomes 3-month after ischemic stroke. Methods: Using prospective stroke registry data, we consecutively enrolled 345 participants with ischemic stroke whose cognitive functions were evaluated 3-month after stroke. Their cognition was assessed with the Korean version of the Vascular Cognitive Impairment Harmonization Standards and the Korean-Mini Mental Status Examination. PSCI was defined as a z-score of < -2 standard deviations for age, sex, and education adjusted means in at least one cognitive domain. The participants were categorized into five groups according to the quintiles of NLR (lowest NLR, Q1). The cross-sectional association between NLR and PSCI was assessed using multiple logistic regression, adjusting for age, sex, education, vascular risk factors, and stroke type. Results: A total of 345 patients were enrolled. The mean age was 63.0 years and the median NIHSS score and NLR were 2 [1-4] and 2.26 [1.65-2.91], respectively. PSCI was identified in 71 (20.6%) patients. NLR was a significant predictor for PSCI both as a continuous variable (adjusted OR, 1.14; 95% CI, 1.00-1.31) and as a categorical variable (Q5, adjusted OR, 3.26; 95% CI, 1.17-9.08). Patients in the Q5 group (NLR ≥ 3.80) showed significantly worse performance in global cognition and in visuospatial and memory domains. Conclusions: NLR in the acute stage of ischemic stroke was independently associated with PSCI at 3 months after stroke, and high NLR was specifically associated with cognitive dysfunction in the memory and visuospatial domains. Thus, systemic inflammation may be a modifiable risk factor that may influence cognitive outcomes after stroke.

Dataset Information

Gut Microbiome Signatures Are Biomarkers for Cognitive Impairment in Patients With Ischemic Stroke.

Publications

Gut Microbiome Signatures Are Biomarkers for Cognitive Impairment in Patients With Ischemic Stroke.

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