Gut Microbiota in Ischemic Stroke: Role of Gut Bacteria-Derived Metabolites.

Ischemic stroke (IS) remains a leading cause of death and long-term disability globally. Several mechanisms including glutamate excitotoxicity, calcium overload, neuroinflammation, oxidative stress, mitochondrial damage, and apoptosis are known to be involved in the pathogenesis of IS, but the underlying pathophysiology mechanisms of IS are not fully clarified. During the past decade, gut microbiota were recognized as a key regulator to affect the health of the host either directly or via their metabolites. Recent studies indicate that gut bacterial dysbiosis is closely related to hypertension, diabetes, obesity, dyslipidemia, and metabolic syndrome, which are the main risk factors for cardiovascular diseases. Increasing evidence indicates that IS can lead to perturbation in gut microbiota and increased permeability of the gut mucosa, known as "leaky gut," resulting in endotoxemia and bacterial translocation. In turn, gut dysbiosis and impaired intestinal permeability can alter gut bacterial metabolite signaling profile from the gut to the brain. Microbiota-derived products and metabolites, such as short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine N-oxide (TMAO), lipopolysaccharides (LPS), and phenylacetylglutamine (PAGln) can exert beneficial or detrimental effects on various extraintestinal organs, including the brain, liver, and heart. These metabolites have been increasingly acknowledged as biomarkers and mediators of IS. However, the specific role of the gut bacterial metabolites in the context of stroke remains incompletely understood. In-depth studies on these products and metabolites may provide new insight for the development of novel therapeutics for IS.

Kitchen Diet vs. Industrial Diets-Impact on Intestinal Barrier Parameters among Stroke Patients.

BACKGROUND AND AIMS: Strokes are the second highest cause of death in the world and the most common cause of permanent disability in adults. Intestinal barrier permeability thus contributes to diminished homeostasis within the body, which further affects the healing process and convalescence. Each stroke patient should be administered with ingredients that support the intestinal barrier (e.g., protein and fiber). The aim of this study was to compare the effect of various types of diet (enteral with or without fiber vs. a mixed kitchen diet) on the metabolic activity of intestinal microbiota, namely short chain fatty acids, and gut barrier integrity parameters (zonulin and calprotectin. METHODS: Patients (n = 59), after suffering an ischemic stroke, were randomly allocated to three groups receiving: the kitchen diet (n = 32; 1.2 g fiber in 100 mL); Nutrison Energy® (n = 14; 0.02 g fiber in 100 mL); and Nutrison Diason Energy HP® (n = 13; 1.8 g fiber in 100 mL). The patients underwent anthropometric measurements and blood samples (for prealbumin measurements), and stool samples (for zonulin and calprotectin determinations) were taken twice, on admission and a week later. RESULTS: Industrial diets enriched with fiber maintained nutritional status and had a beneficial effect on intestinal barrier permeability parameters. Patients fed with kitchen diets demonstrated a decreased number of lymphocytes, hemoglobin, erythrocytes, and increased serum concentration of C-reactive protein, but improved gut barrier markers. Proton pump inhibitors were shown to increase the inflammatory process in gut. CONCLUSIONS: Stroke patients should be administered with industrial diets enriched with fiber to improve gut barrier integrity and nutritional parameters.

Gut Microbiota and Their Metabolites in Stroke: A Double-Edged Sword.

Besides damaging the brain, stroke causes systemic changes, including to the gastrointestinal system. A growing body of evidence supports the role of the gut and its microbiota in stroke, stroke prognosis, and recovery. The gut microbiota can increase the risk of a cerebrovascular event, playing a role in the onset of stroke. Conversely, stroke can induce dysbiosis of the gut microbiota and epithelial barrier integrity. This has been proposed as a contributor to systemic infections. In this review, we describe the role of the gut microbiota, microbiome and microbiota-derived metabolites in experimental and clinical stroke, and their potential use as therapeutic targets. Fourteen clinical studies have identified 62 upregulated (eg, Streptococcus, Lactobacillus, Escherichia) and 29 downregulated microbial taxa (eg, Eubacterium, Roseburia) between stroke and healthy participants. The majority found that stroke patients have reduced gut microbiome diversity. However, other nonbacterial microorganisms are yet to be studied. In experimental stroke, severity is dependent on gut microbiome composition, whereas the latter can greatly change with antibiotics, age, and diet. Consumption of foods rich in choline and L-carnitine are positively associated with stroke onset via production of trimethylamine N-oxide in experimental and clinical stroke. Conversely, in mice, consumption of dietary fiber improves stroke outcome, likely via gut microbiota-derived metabolites called short-chain fatty acids, such as acetate, propionate, and butyrate. The majority of the evidence, however, comes from experimental studies. Clinical interventions targeted at gut microbiota-derived metabolites as new therapeutic opportunities for stroke prevention and treatment are warranted.

Distinctive Gut Microbiota Alteration Is Associated with Poststroke Functional Recovery: Results from a Prospective Cohort Study.

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.

Compositional and functional alterations of gut microbiota in patients with stroke.

BACKGROUND AND AIMS: There is accumulating evidence that gut microbiota plays a key role in cardiovascular diseases. Gut bacteria can transform dietary choline, l-carnitine, and trimethylamine N-oxide (TMAO) into trimethylamine, which can be oxidized into TMAO again in the liver. However, the alterations of the gut microbiota in large artery atherosclerotic (LAA) stroke and cardioembolic (CE) stroke have been less studied. METHODS AND RESULTS: We performed a case-control study in patients with LAA and CE types of strokes. We profiled the gut microbiome using Illumina sequencing of the 16S ribosomal RNA gene (V4-V5 regions), and TMAO was determined via liquid chromatography-tandem mass spectrometry. Our results showed that the TMAO levels in the plasma of patients with LAA and CE strokes were significantly higher than those in controls (LAA stroke, 2931 ± 456.4 ng/mL; CE stroke, 4220 ± 577.6 ng/mL; healthy control, 1663 ± 117.8 ng/mL; adjusted p < 0.05). The TMAO level in the plasma of patients with LAA stroke was positively correlated with the carotid plaque area (rho = 0.333, 95% CI = 0.08-0.55, p = 0.0093). Notably, the composition and the function of gut microbiota in the LAA stroke group were significantly different from those in the control group (FDR-adjusted p-value < 0.05). There was no significant association between gut microbiota and CE stroke in our study. CONCLUSION: This study provides evidence for significant compositional and functional alterations of the gut microbiome in patients with LAA stroke. Gut microbiota might serve as a potential biomarker for patients with LAA stroke.

Potential Benefits of Probiotics and Prebiotics for Coronary Heart Disease and Stroke.

Among cardiovascular diseases (CVDs), a major cause of morbidity and mortality worldwide, coronary heart disease and stroke are the most well-known and extensively studied. The onset and progression of CVD is associated with multiple risk factors, among which, gut microbiota has received much attention in the past two decades. Gut microbiota, the microbial community colonizing in the gut, plays a prominent role in human health. In particular, gut dysbiosis is directly related to many acute or chronic dysfunctions of the cardiovascular system (CVS) in the host. Earlier studies have demonstrated that the pathogenesis of CVD is strongly linked to intestinal microbiota imbalance and inflammatory responses. Probiotics and prebiotics conferring various health benefits on the host are emerging as promising therapeutic interventions for many diseases. These two types of food supplements have the potential to alleviate the risks of CVD through improving the levels of several cardiovascular markers, such as total and low-density lipoprotein (LDL) cholesterol, high sensitivity C-reactive protein (hs-CRP), and certain cytokines involved in the inflammatory response. In this review, we focus mainly on the preventive effects of probiotics and prebiotics on CVD via rebalancing the structural and functional changes in gut microbiota and maintaining immune homeostasis.

Gut microbes impact stroke severity via the trimethylamine N-oxide pathway.

Clinical studies have demonstrated associations between circulating levels of the gut-microbiota-derived metabolite trimethylamine-N-oxide (TMAO) and stroke incident risk. However, a causal role of gut microbes in stroke has not yet been demonstrated. Herein we show that gut microbes, through dietary choline and TMAO generation, directly impact cerebral infarct size and adverse outcomes following stroke. Fecal microbial transplantation from low- versus high-TMAO-producing human subjects into germ-free mice shows that both TMAO generation and stroke severity are transmissible traits. Furthermore, employing multiple murine stroke models and transplantation of defined microbial communities with genetically engineered human commensals into germ-free mice, we demonstrate that the microbial cutC gene (an enzymatic source of choline-to-TMA transformation) is sufficient to transmit TMA/TMAO production, heighten cerebral infarct size, and lead to functional impairment. We thus reveal that gut microbiota in general, specifically the metaorganismal TMAO pathway, directly contributes to stroke severity.

Rhinocerebral mucormycosis in COVID-19 patient with diabetes a deadly trio: Case series from the north-western part of India.

Coronavirus disease 2019 (COVID-19), may present with a myriad of clinical manifestations and complications. Patients with COVID-19 are at increased risk of pulmonary thromboembolism, acute cardiac injury, arrhythmias, acute stroke, and secondary infections. Mucormycosis is a catastrophic fungal infection characterized by vascular invasion, thrombosis, and necrosis of tissues. We report five cases of COVID-19 infection, who developed rhino-orbital mucormycosis, during the course of treatment. Early recognition of this life-threatening infection is the key to allow for optimal treatment and improved outcomes.

Comparison of mortality, stroke, and relapse for methicillin-resistant versus methicillin-susceptible Staphylococcus aureus infective endocarditis: a retrospective cohort study.

The purpose of this study was to compare survival, relapse, and stroke for patients with methicillin-resistant Staphylococcus aureus (MRSA) vs methicillin-susceptible S. aureus (MSSA) infective endocarditis (IE). In this retrospective study, the primary outcome of death and secondary outcomes of stroke and relapse were compared using multivariable Cox proportional hazards regression. Surgical treatment was adjusted for as a time-dependent variable. In total, 355 patients with at least one episode of IE caused by S. aureus were included. Patients with MRSA IE had higher mortality than those with MSSA IE (HR 1.34, 95% CI 1.01-1.77), but did not have a higher risk of stroke (HR 0.75, 95% CI 0.43-1.32) or relapse (HR 0.89, 95% CI 0.26-3.05). The cumulative incidence of relapse was very small. Among patients with IE caused by S. aureus MRSA infection is associated with higher mortality than MSSA infection.

Post-injury immunosuppression and secondary infections are caused by an AIM2 inflammasome-driven signaling cascade.

Loss of lymphocytes, particularly T cell apoptosis, is a central pathological event after severe tissue injury that is associated with increased susceptibility for life-threatening infections. The precise immunological mechanisms leading to T cell death after acute injury are largely unknown. Here, we identified a monocyte-T cell interaction driving bystander cell death of T cells in ischemic stroke and burn injury. Specifically, we found that stroke induced a FasL-expressing monocyte population, which led to extrinsic T cell apoptosis. This phenomenon was driven by AIM2 inflammasome-dependent interleukin-1ß (IL-1ß) secretion after sensing cell-free DNA. Pharmacological inhibition of this pathway improved T cell survival and reduced post-stroke bacterial infections. As such, this study describes inflammasome-dependent monocyte activation as a previously unstudied cause of T cell death after injury and challenges the current paradigms of post-injury lymphopenia.

Cardiac thrombus and stroke in a child with Mycoplasma pneumoniae pneumonia: A case report.

RATIONALE: Cardiac thrombus and stroke are rare complications in Mycoplasma pneumoniae infection, which is a common cause of community-acquired pneumonia in children. Early detection and prevention of thrombus in children with M pneumoniae pneumonia is relatively difficult. PATIENT CONCERNS: A 5-year-old boy with severe M pneumoniae pneumonia was referred to our center. During the treatment with sufficient antibiotics, an echocardiography surprisingly revealed a thrombus in the left atrium, with significant changes in D-dimer level and anti-phospholipid antibodies. At day 12 after admission, the patient showed impaired consciousness, aphasia, and reduced limb muscle power. Magnetic resonance angiography (MRA) showed right middle cerebral artery infarction. DIAGNOSES: Cardiac thrombus and stroke associated with M pneumoniae pneumonia. INTERVENTIONS: He was started on aggressive antibiotic therapy and urokinase thrombolytic therapy for 24 hours, continued with low molecular heparin calcium and aspirin along with rehabilitation training. OUTCOMES: On follow up, the D-dimer decreased slowly and echocardiograms showed a steadily decreasing size of thrombus with eventual disappearance at day 22 after admission. His left limb muscle power was improved after rehabilitation for 2 months. LESSONS: Early diagnosis and treatment with multiple modalities maybe useful for improving prognosis of cardiac thrombus and stroke in M pneumoniae pneumonia. Changes in D-dimer level and anti-phospholipid antibodies should be routinely monitored in severe M pneumoniae pneumonia.

The Effect and Mechanism of Exercise Training on Rats with Poststroke Depression Based on the Intestinal Flora.

Depression of poststroke depression (PSD) is the most common neuropsychiatric complication after stroke. Patients with PSD had higher mortality, more cognitive disorder, lower quality of life, and higher suicidal tendency. The pathogenesis of PSD mainly involves neurotransmitter inflammatory factors, HPA and BDNF. Enteral dysfunction and intestinal flora disorders caused by stroke can participate in the pathogenesis of PSD through various ways, such as immune, endocrine, and nervous system. In this experiment, we used exercise training as an intervention means to explore the curative effect and possible mechanism by observing the changes of behavior, inflammatory factors, and intestinal flora in rats. The results show that the mechanism of exercise training to improve the depressive behavior of rats may be related to inhibiting the expression of proinflammatory factors and increasing the number of lactic acid bacteria in the intestine.

Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention.

Acute central nervous system (CNS) injuries, including stroke, traumatic brain injury (TBI), and spinal cord injury (SCI), are the common causes of death or lifelong disabilities. Research into the role of the gut microbiota in modulating CNS function has been rapidly increasing in the past few decades, particularly in animal models. Growing preclinical and clinical evidence suggests that gut microbiota is involved in the modulation of multiple cellular and molecular mechanisms fundamental to the progression of acute CNS injury-induced pathophysiological processes. The altered composition of gut microbiota after acute CNS injury damages the equilibrium of the bidirectional gut-brain axis, aggravating secondary brain injury, cognitive impairments, and motor dysfunctions, which leads to poor prognosis by triggering pro-inflammatory responses in both peripheral circulation and CNS. This review summarizes the studies concerning gut microbiota and acute CNS injuries. Experimental models identify a bidirectional communication between the gut and CNS in post-injury gut dysbiosis, intestinal lymphatic tissue-mediated neuroinflammation, and bacterial-metabolite-associated neurotransmission. Additionally, fecal microbiota transplantation, probiotics, and prebiotics manipulating the gut microbiota can be used as effective therapeutic agents to alleviate secondary brain injury and facilitate functional outcomes. The role of gut microbiota in acute CNS injury would be an exciting frontier in clinical and experimental medicine.

A rare infective cause of stroke in an immunocompetent child.

BACKGROUND: Infections are a common cause of childhood stroke with variable presentation. The current case describes a rare infective cause of venous and arterial stroke in an immunocompetent girl with management implications. CASE DESCRIPTION: A 12 year old girl, presented with history of fever for 10 days, painful swelling of right eye for 7 days and altered sensorium for 2 days. On examination, she had right eye orbital cellulitis and fullness of right paranasal area. On nervous system examination, she was delirious, had right eye ophthalmoparesis, left upper motor neuron facial palsy and signs of meningeal inflammation. Her contrast enhanced CT head and subsequent MRI brain with arteriography and venography revealed right cavernous sinus and distal internal carotid artery thrombosis. She was started on intravenous ceftriaxone and vancomycin and subcutaneous heparin. In view of persistent symptoms, endoscopic debridement of right nasal cavity was done, which showed growth of aspergillus flavus. Subsequently, she was started on intravenous voriconazole. Within a week, she was afebrile, her inflammatory and neurological signs started improving. She was discharged after 3 weeks of intravenous voriconazole which was continued for 3 more weeks orally. Her procoagulant and immunodeficiency work up were normal. At 4 months follow up, she showed both clinical and radiological resolution. CONCLUSIONS: Despite high mortality described in sino-orbital aspergillosis, early and appropriate treatment led to optimal outcome. In deep seated infections, isolation of etiological organism should be attempted, particularly when patient doesn't respond to conventional antimicrobial therapy.

The Gut Ecosystem: A Critical Player in Stroke.

The intestinal microbiome is emerging as a critical factor in health and disease. The microbes, although spatially restricted to the gut, are communicating and modulating the function of distant organs such as the brain. Stroke and other neurological disorders are associated with a disrupted microbiota. In turn, stroke-induced dysbiosis has a major impact on the disease outcome by modulating the immune response. In this review, we present current knowledge on the role of the gut microbiome in stroke, one of the most devastating brain disorders worldwide with very limited therapeutic options, and we discuss novel insights into the gut-immune-brain axis after an ischemic insult. Understanding the nature of the gut bacteria-brain crosstalk may lead to microbiome-based therapeutic approaches that can improve patient recovery.

Management of Large Vessel Occlusion Stroke Related to Infective Endocarditis: Is Mechanical Thrombectomy a Safe Option?

INTRODUCTION: Acute ischemic stroke is the most common neurological complication of infective endocarditis. Intravenous thrombolysis is contraindicated in these patients due to a higher risk of hemorrhagic complications. Whether mechanical thrombectomy has some benefit in these patients remains unanswered although some favorable results can be found in literature. METHODS: We report twelve cases of acute ischemic stroke due to septic emboli treated with mechanical thrombectomy in two comprehensive stroke centers. RESULTS: Median age was 63 years (IQR 58.8-77.5 years). Diagnosis of infective endocarditis was previous to the diagnosis of stroke in three of the patients. There were five cases of prosthetic-valve endocarditis and eight cases of native-valve endocarditis. Two patients were treated with intravenous thrombolysis with an extensive subarachnoid hemorrhage in 24 h follow-up CT in one of them. Another patient suffered an arterial perforation during the endovascular procedure without successful recanalization. 6 of the patients (50%) developed some type of hemorrhagic complications with three cases of symptomatic intracerebral hemorrhage. Early neurological recovery was achieved in 3 (25%) patients. Functional independence at 3 months in patients with successful revascularization was reached in 50% of the cases. CONCLUSIONS: In patients with large vessel acute ischemic stroke related to infective endocarditis, mechanical thrombectomy might be considered with some potential benefit reported. There may be a high risk of hemorrhagic complications, as known for intravenous thrombolysis in this condition, suggesting that this procedure should be carefully evaluated in these patients.

Association between periodontal disease due to Campylobacter rectus and cerebral microbleeds in acute stroke patients.

Oral health conditions and cerebral small vessel disease, such as white matter lesions or cerebral microbleeds (CMBs), are associated with the incidence of stroke. The purpose of this study was to examine the associations between oral health conditions (serum IgG titers of periodontal pathogens) with the presence or severity of CMBs in acute stroke patients. From January 2013 to April 2016, acute stroke patients were registered in two hospitals. Serum samples were evaluated for antibody titers against 9 periodontal pathogens using the ELISA method. The cut-off points for reactivity (the positive decision point) to each antigen were defined as more than a mean ELISA unit + 1 standard deviation (after logarithmic transformation) in all subjects. CMBs were evaluated on T2*-weighted MRI. In all, 639 patients were evaluated (ischemic, n = 533 and hemorrhagic, n = 106; 73.1 ± 12.9 years old). Among these patients, 627 were available for CMB evaluation. Among the 9 evaluated periodontal pathogens, only Campylobacter rectus (C. rectus) was associated with the presence of CMBs. the prevalence of positive serum antibody titers against C. rectus was higher among patients with CMBs than among those without CMBs (14.6% vs. 8.7%, P = 0.025). In addition, positive serum antibody titers against C. rectus remained one of the factors associated with the presence of CMBs in multivariate logistic analysis (odds ratio 2.03, 95% confidence interval 1.19-3.47, P = 0.010). A positive serum antibody titer against C. rectus was associated with the presence of CMBs in acute stroke patients.

Serum IgG titers to periodontal pathogens predict 3-month outcome in ischemic stroke patients.

Several cohort studies have shown that periodontal disease is associated with an increased risk for stroke. However, it remains unclear whether serum antibody titers for a specific periodontal pathogen are associated with outcome after ischemic stroke, and which kinds of pathogens are associated with ischemic stroke. We examined the relationship between serum IgG titers to periodontal pathogens and outcome in ischemic stroke patients. A total of 445 patients with acute ischemic stroke (194 female [44.0%], mean age 71.9±12.3 years) were registered in this study. Serum IgG titers to 9 periodontal pathogens (Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Prevotella nigrescens, Fusobacterium nucleatum, Treponema denticola, Tannerella forsythensis, Campylobacter rectus, Eikenella corrodens) were evaluated using the enzyme-linked immunosorbent assay (ELISA) method. An unfavorable outcome was defined as a 3 or higher on the modified Rankin Scale. The proportion of patients with unfavorable outcome was 25.4% (113 patients). Based on multivariate logistic regression analysis, numbers of IgG antibodies positive for periodontal pathogens (odds ratio 1.20, 95% CI 1.02-1.41, p = 0.03) were independent predictors of unfavorable outcome in ischemic stroke patients.

Distinct Commensal Bacterial Signature in the Gut Is Associated With Acute and Long-Term Protection From Ischemic Stroke.

Background and Purpose- Commensal gut bacteria have a profound impact on stroke pathophysiology. Here, we investigated whether modification of the microbiota influences acute and long-term outcome in mice subjected to stroke. Methods- C57BL/6 male mice received a cocktail of antibiotics or single antibiotic. After 4 weeks, fecal bacterial density of the 16S rRNA gene was quantitated by qPCR, and phylogenetic classification was obtained by 16S rRNA gene sequencing. Infarct volume and hemispheric volume loss were measured 3 days and 5 weeks after middle cerebral artery occlusion, respectively. Neurological deficits were tested by the Tape Test and the open field test. Results- Mice treated with a cocktail of antibiotics displayed a significant reduction of the infarct volume in the acute phase of stroke. The neuroprotective effect was abolished in mice recolonized with a wild-type microbiota. Single antibiotic treatment with either ampicillin or vancomycin, but not neomycin, was sufficient to reduce the infarct volume and improved motorsensory function 3 days after stroke. This neuroprotective effect was correlated with a specific microbial population rather than the total bacterial density. In particular, random forest analysis trained for the severity of the brain damage revealed that Bacteroidetes S24.7 and the enzymatic pathway for aromatic metabolism discriminate between large versus small infarct size. Additionally, the microbiota signature in the ampicillin-treated mice was associated with a reduced gut inflammation, long-term favorable outcome shown by an amelioration of the stereotypic behavior, and a reduction of brain tissue loss in comparison to control and was predictive of a regulation of short-chain fatty acids and tryptophan pathways. Conclusions- The findings highlight the importance of the intestinal microbiota in short- and long-term outcomes of ischemic stroke and raises the possibility that targeted modification of the microbiome associated with specific microbial enzymatic pathways may provide a preventive strategy in patients at high risk for stroke. Visual Overview- An online visual overview is available for this article.