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.

Identification of Gut Microbiome Signatures in Patients With Post-stroke Cognitive Impairment and Affective Disorder

“…It is found that Lachnospiraceae dynamically changed with age and positively correlated with anxiety and cognition levels (Duan et al, 2019 ; Tengeler et al, 2020 ; Liu et al, 2021 ). The abundance of Lachnospiraceae is significantly decreased in the age-matched PSCI patients (Ling et al, 2020 ). Moreover, Lachnospiraceae had a potential diagnostic value for patients with acute ischemic ST (Xiang et al, 2020 ).…”

ZiBuPiYin Recipe Prevented and Treated Cognitive Decline in ZDF Rats With Diabetes-Associated Cognitive Decline via Microbiota–Gut–Brain Axis Dialogue

“…It is speculated that the gut microbiota plays an important role in regulating the metabolic pathways of the host and plays an important role in a variety of disease phenotypes Leclercq et al, 2020;Ling et al, 2020;Shi et al, 2020b;van Soest et al, 2020). In recent years, people have realized that the microbiota-gut-brain axis is a novel concept in the field of neurological disease research (Li et al, 2020;Mao et al, 2020;FIGURE 9 | Schematic diagram showing the regulation of ZBPYR treatment on the network of differentiated bacterial and metabolite structural components.…”

Rehabilitation and Biomarkers of Stroke Recovery: Study Protocol for a Randomized Controlled Trial

“…Evaluation endpoints of WP4 include incidence of psychopathology (e.g., anxiety and depression) after stroke and related pain conditions, psychopathological issues, and coping strategies affecting adherence to rehabilitation programs, effectiveness of psychopharmacological and psychotherapeutic treatments in stroke patients, definition of specific psychological interventions supporting rehabilitation ( 17 , 18 ). Accordingly, the outcomes considered are the Symptom Checklist-90 scale ( 19 ); the Eysenck Personality Questionnaire-R ( 20 ); the COPE scale ( 21 ); the General Self-Efficacy Scale ( 22 ); the Acceptance and Action Questionnaire-II scale ( 23 ); the Multidimensional Scale of Perceived Social Support ( 24 ); the Brief Pain Inventory-I scale ( 25 ).…”

“…To identify bacterial species, present in GM, analysis of nine variable regions of 16S ribosomal RNA gene will be performed by next generation sequencing (NGS). Bioinformatical and statistical analyses will be conducted to relate gut microbiota signatures at different taxonomic levels to stroke rehabilitation conditions ( 25 ).…”