Background: Significant dysbiosis occurs in the gut microbiome of stroke patients. Condensing these broad, complex changes into one index would greatly facilitate the clinical usage of gut microbiome data. Here, we formulated a gut microbiota index in patients with acute ischemic stroke based on their gut microbiota dysbiosis patterns and tested whether the index was correlated with brain injury and early outcome. Methods: A total of 104 patients with acute ischemic stroke and 90 healthy individuals were recruited, and their gut microbiotas were compared and to model a Stroke Dysbiosis Index (SDI), which representing stroke-associated dysbiosis patterns overall. Another 83 patients and 70 controls were recruited for validation. The association of SDI with stroke severity (National Institutes of Health Stroke Scale [NIHSS] score) and outcome (modified Rankin scale [mRS] score: favorable, 0–2; unfavorable, >2) at discharge was also assessed. A middle cerebral artery occlusion (MCAO) model was used in human flora-associated (HFA) animals to explore the causal relationship between gut dysbiosis and stroke outcome. Results: Eighteen genera were significantly different between stroke patients and healthy individuals. The SDI formula was devised based on these microbiome differences; SDI was significantly higher in stroke patients than in healthy controls. SDI alone discriminated stroke patients from controls with AUCs of 74.9% in the training cohort and 84.3% in the validation cohort. SDI was significantly and positively correlated with NIHSS score on admission and mRS score at discharge. Logistic regression analysis showed that SDI was an independent predictor of severe stroke (NIHSS ≥8) and early unfavorable outcome (mRS >2). Mice receiving fecal transplants from high-SDI patients developed severe brain injury with elevated IL-17 + γδ T cells in gut compared to mice receiving transplants from low-SDI patients (all P < 0.05). Conclusions: We developed an index to measure gut microbiota dysbiosis in stroke patients; this index was significantly correlated with patients' outcome and was causally related to outcome in a mouse model of stroke. Our model facilitates the potential clinical application of gut microbiota data in stroke and adds quantitative evidence linking the gut microbiota to stroke.

Background The intestinal microbiota and its metabolites have been reported to play an important role in stroke. Gut microbiota–originating short‐chain fatty acids (SCFAs) modulate brain functions directly or indirectly through immune, endocrine, vagal, and other humoral pathways. However, relatively few investigations have evaluated the gut microbiome and SCFAs spectrum or their potential associations with stroke outcomes in acute ischemic stroke (AIS) patients with different stroke severities. Methods We used 16S rRNA gene sequencing and gas chromatography to compare the fecal microbial composition and SCFA spectrum between AIS patients (n = 140) and healthy controls (n = 92). Their associations with 90‐day poor functional outcomes were evaluated by logistic regression models. Results We found that the intestinal microbiota distinguished AIS patients from healthy controls. A lack of SCFAs‐producing bacteria and a low fecal SCFAs level defined dysbiosis in AIS patients, especially those with increased stroke severity. The SCFAs levels were negatively correlated with stroke severity and prognosis. Reduced SCFAs levels, especially acetate, were associated with an increased risk of 90‐day poor functional outcomes even after adjustments. Conclusions Dysbiosis of SCFAs‐producing bacteria and SCFAs in AIS patients increased the subsequent risk for poor functional outcomes, indicating that SCFAs could be potential prognostic markers and therapeutic targets for stroke.

Objective: Gut microbiota is a newly identified risk factor for stroke, and there are no large prospective studies linking the baseline gut microbiome to long-term risk of stroke. We present here the correlation between the gut microbiota and stroke risk in people with no prior stroke history.Methods: A total of 141 participants aged ≥60 years without prior history of stroke were recruited and divided into low-risk, medium-risk, and high-risk groups based on known risk factors and whether they were suffering from chronic diseases. The composition of their gut microbiomes was compared using 16S rRNA gene amplicon next-generation-sequencing and Quantitative Insights into Microbial Ecology (QIIME) analysis. Levels of fecal short-chain fatty acids were measured using gas chromatography.Results: We found that opportunistic pathogens (e.g., Enterobacteriaceae and Veillonellaceae) and lactate-producing bacteria (e.g., Bifidobacterium and Lactobacillus) were enriched, while butyrate-producing bacteria (e.g., Lachnospiraceae and Ruminococcaceae) were depleted, in the high-risk group compared to the low-risk group. Butyrate concentrations were also lower in the fecal samples obtained from the high-risk group than from the low-risk group. The concentrations of other short-chain fatty acids (e.g., acetate, propionate, isobutyrate, isovalerate, and valerate) in the gut were comparable among the three groups.Conclusion: Participants at high risk of stroke were characterized by the enrichment of opportunistic pathogens, low abundance of butyrate-producing bacteria, and reduced concentrations of fecal butyrate. More researches into the gut microbiota as a risk factor in stroke should be carried out in the near future.