Microbiota in cerebrovascular disease: A key player and future therapeutic target

Tonomura, Shuichi; Ihara, Masafumi; Friedland, Robert P.

doi:10.1177/0271678x20918031

Cited by 32 publications

(29 citation statements)

References 121 publications

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“…The increase in Coriobacteriaceae observed in this study may be the result of compensatory mechanisms in response to stroke-induced changes in gastrointestinal conditions that alter the microbial ecology throughout the gut. Understanding the role of microflora on the regulation of metabolites associated with stroke may provide an insight on the development of novel therapeutic targets, as reviewed by Tonomura et al (2020) indicating the role of bacterial metabolites such as TAMO and short-chain fatty acids in stroke.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Changes in the Gut Microbiome at the Acute Stage of Ischemic Stroke in a Pig Model

et al. 2020

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Stroke is a major cause of death and long-term disability affecting seven million adults in the United States each year. Recently, it has been demonstrated that neurological diseases, associated pathology, and susceptibility changes correlated with changes in the gut microbiota. However, changes in the microbial community in stroke has not been well characterized. The acute stage of stroke is a critical period for assessing injury severity, therapeutic intervention, and clinical prognosis. We investigated the changes in the gut microbiota composition and diversity using a middle cerebral artery (MCA) occlusion ischemic stroke pig model. Ischemic stroke was induced by cauterization of the MCA in pigs. Blood samples were collected prestroke and 4 h, 12 h, 1 day, and 5 days poststroke to evaluate circulating proinflammatory cytokines. Fecal samples were collected prestroke and 1, 3, and 5 days poststroke to assess gut microbiome changes. Results showed elevated systemic inflammation with increased plasma levels of tumor necrosis factor alpha at 4 h and interleukin-6 at 12 h poststroke, relative to prestroke. Microbial diversity and evenness were reduced at 1 day poststroke compared to prestroke. Microbial diversity at 3 days poststroke was negatively correlated with lesion volume. Moreover, beta-diversity analysis revealed trending overall differences over time, with the most significant changes in microbial patterns observed between prestroke and 3 days poststroke. Abundance of the Proteobacteria was significantly increased, while Firmicutes decreased at 3 days poststroke, compared to prestroke populations. Abundance of the lactic acid bacteria Lactobacillus was reduced at 3 days poststroke. By day 5, the microbial pattern returned to similar values as prestroke, suggesting the plasticity of gut microbiome in an acute period of stroke in a pig model. These findings provide a basis for characterizing gut microbial changes during the acute stage of stroke, which can be used to assess stroke pathology and the potential development of therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Dynamic Changes in the Gut Microbiome at the Acute Stage of Ischemic Stroke in a Pig Model

et al. 2020

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“…Even so, it is complicated to establish if microbiota alterations are a cause, consequence or simply an adaptation to the pathological conditions of the individual [ 137 , 138 ]. Regardless, there are ever more studies contemplating the therapeutic validity of microbiota, in order to treat several complications [ 139 , 140 ], elucidating the importance of focusing our insights towards the study of gut microbiota, particularly a better understanding and management of health and disease.…”

Section: Understanding the Role Of Human Gut Microbiotamentioning

confidence: 99%

Type 2 Diabetes Mellitus Associated with Obesity (Diabesity). The Central Role of Gut Microbiota and Its Translational Applications

et al. 2020

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Obesity is a condition of rising prevalence worldwide, with important socioeconomic implications, being considered as a growing public health concern. Frequently, obesity brings other complications in addition to itself—like Type 2 Diabetes Mellitus (T2DM)—sharing origin, risk factors and pathophysiological mechanisms. In this context, some authors have decided to include both conditions as a unique entity known as “diabesity”. In fact, understanding diabesity as a single disease is possible to maximise the benefits from therapies received in these patients. Gut microbiota plays a key role in individual’s health, and their alterations, either in its composition or derived products are related to a wide range of metabolic disorders like T2DM and obesity. The present work aims to collect the different changes reported in gut microbiota in patients with T2DM associated with obesity and their possible role in the onset, development, and establishment of the disease. Moreover, current research lines to modulate gut microbiota and the potential clinical translation derived from the knowledge of this system will also be reviewed, which may provide support for a better clinical management of such a complex condition.

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“…Nevertheless, evidence has accumulated in the past decade that link the gut microbiome to cardiovascular diseases, [9][10][11] and neurological and behavioral disorders. [12][13][14][15][16][17][18] In this study, we tested the hypothesis that the gut microbiome has a major role in the disruption of the BBB in the spontaneously hypertensive stroke prone rat (SHRSP), an animal model for CSVD. We focus on the BBB since it appears to be an early and important event leading to the subsequent pathological sequela in CVSD.…”

Section: Introductionmentioning

confidence: 99%

The gut microbiome contributes to blood‐brain barrier disruption in spontaneously hypertensive stroke prone rats

et al. 2021

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In recent years, it has become apparent that the gut microbiome can influence the functioning and pathological states of organs and systems throughout the body. In this study, we tested the hypothesis that the gut microbiome has a major role in the disruption of the blood-brain barrier (BBB) in the spontaneously hypertensive stroke prone rats (SHRSP), an animal model for hypertensive cerebral small vessel disease (CSVD). Loss of BBB is thought to be an early and initiating component to the full expression of CSVD in animal models and humans. To test this hypothesis, newly born SHRSP pups were placed with foster dams of the SHRSP strain or dams of the WKY strain, the control strain that does not demonstrate BBB dysfunction or develop hypertensive CSVD. Similarly, WKY pups were placed with foster dams of the same or opposite strain. The rationale for cross fostering is that the gut microbiomes are shaped by environmental bacteria of the foster dam and the nesting surroundings.Analysis of the bacterial genera in feces, using 16S rRNA analysis, demonstrated that the gut microbiome in the rat pups was influenced by the foster dam. SHRSP offspring fostered on WKY dams had systolic blood pressures (SBPs) that were significantly decreased by 26 mmHg (P < .001) from 16-20 weeks, compared to SHRSP offspring fostered on SHRSP dams. Similarly WKY offspring fostered on SHRSP dams had significantly increased SBP compared to WKY offspring fostered on WKY dams, although the magnitude of SBP change was not as robust. At ~20 weeks of age, rats fostered on SHRSP dams showed enhanced inflammation in distal ileum regardless of the strain of the offspring. Disruption of BBB integrity, an early marker of CSVD onset, was improved in SHRSPs that were fostered on WKY dams when compared to the SHRSP rats fostered on SHRSP dams. Although SHRSP is a genetic model for CSVD, environmental factors such as the gut microbiota of the foster dam have a major influence in the loss of BBB integrity.

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Microbiota in cerebrovascular disease: A key player and future therapeutic target

Cited by 32 publications

References 121 publications

Dynamic Changes in the Gut Microbiome at the Acute Stage of Ischemic Stroke in a Pig Model

Dynamic Changes in the Gut Microbiome at the Acute Stage of Ischemic Stroke in a Pig Model

Type 2 Diabetes Mellitus Associated with Obesity (Diabesity). The Central Role of Gut Microbiota and Its Translational Applications

The gut microbiome contributes to blood‐brain barrier disruption in spontaneously hypertensive stroke prone rats

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