Objectives. Functional prognosis is potentially correlated with gut microbiota alterations following the dysregulation of the gut-microbiota-brain axis after stroke. This study was designed to explore the poststroke alterations of gut microbiota and potential correlations between gut microbiota and global functions. Methods. A total of thirty-eight patients with stroke and thirty-five healthy demographics-matched controls were recruited. Their fecal DNAs were extracted, and the V3-V4 regions of the conserved bacterial 16S RNA were amplified and sequenced on the Illumina MiSeq platform. Microbial composition, diversity indices, and species cooccurrence were compared between groups. Random forest and receiver operating characteristic analysis were used to identify potential diagnostic biomarkers. Relationships between discriminant bacteria and poststroke functional outcomes were estimated. Results. Higher alpha diversity of gut microbiota was observed in poststroke patients as compared to the healthy controls ( p < 0.05 ). Beta diversity showed that microbiota composition in the poststroke group was significantly different from that in the control group. Relative abundance of nine genera increased significantly in poststroke patients, while 82 genera significantly decreased ( p < 0.05 ). The accuracy, specificity, and susceptibility of the optimal model consisted of the top 10 discriminant species were 93%, 100%, and 86%, respectively. Subgroup analysis showed that bacterial taxa abundant between subacute and chronic stroke patients were overall different ( p < 0.05 ). The modified Rankin scale (mRS) ( r = − 0.370 , p < 0.05 ), Fugl-Meyer assessment (FMA) score ( r = 0.364 , p < 0.05 ), water swallow test (WST) ( r = 0.340 , p < 0.05 ), and Barthel index (BI) ( r = 0.349 , p < 0.05 ) were significantly associated with alterations of distinctive gut microbiota. Conclusions. The gut microbiota in patients with stroke was significantly changed in terms of richness and composition. Significant associations were detected between alterations of distinctive gut microbiota and global functional prognosis. It would facilitate novel treatment target selection in the context of stroke while the causal relationships between distinctive gut microbiota alterations and functional variations need to be further verified with well-designed studies.
Objective The purpose of this study is to investigate the optimal time window for initiating mobilizing after acute ischemic stroke. Methods The TIME trial is a pragmatic, investigator-initiated, multi-center, randomized, 3-arm parallel group, clinical trial. This trial will be conducted in 57 general hospitals in mainland China affiliated with the China Stroke Databank Center and will enroll 6,033 eligible patients with acute ischemic stroke. Participants will be randomly allocated to either (1) the very early mobilization group in which mobilization is initiated within 24 hours from stroke onset, (2) the early mobilization group in which mobilization begins between 24 and 72 hours poststroke, or (3) the late mobilization group in which mobilization is started after 72 hours poststroke. The mobilization protocol is otherwise standardized and identical for each comparison group. Mobilization is titrated by baseline mobility level and progress of patients throughout the intervention period. The primary outcome is death or disability assessed with the modified Rankin scale at 3 months poststroke. Secondary outcomes include impairment score of the National Institutes of Health Stroke Scale, dependence in activities of daily living as measured using the modified Barthel Index, cognitive ability assessed with the Mini-Mental State Examination, incidence of adverse events, hospital length of stay, and total medical costs. Conclusions The TIME trial is designed to answer the question “when is the best time to start mobilization after stroke?” The effect of timing is isolated from the effect of type and dose of mobilization by otherwise applying a standard mobilization protocol across groups. The TIME trial may, therefore, contribute to increasing the knowledge base regarding the optimal time window for initiating mobilization after acute ischemic stroke.
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