Reproductive Senescence and Ischemic Stroke Remodel the Gut Microbiome and Modulate the Effects of Estrogen Treatment in Female Rats

Park, Min J.; Pilla, Rachel; Panta, Aditya; Pandey, Sivani; Sarawichitr, Benjamin; Suchodolski, Jan S.; Sohrabji, Farida

doi:10.1007/s12975-019-00760-5

Cited by 45 publications

(47 citation statements)

References 87 publications

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“…2F). This is consistent with our previous study that the F:B ratio is not changed after stroke in young females (Park et al, 2019a) and the current data suggests that this may be a feature of young animals.…”

Section: Sex Differences In Bacterial Diversitysupporting

confidence: 94%

“…Similarly, young female rats have better stroke outcomes than middle-aged acyclic females and our recent work showed a constitutive difference in bacterial diversity and the F:B ratio at baseline in these two groups. After stroke, however, young females appeared more resilient and less susceptible to changes in the biome, while middle-aged female rat showed elevated F:B ratio and a significant reduction in bacterial diversity (Park et al, 2019b). Collectively, the present data indicate that females may be in overall better health at baseline, allowing them to emerge with a less severe outcome after stroke.…”

Section: Discussionmentioning

confidence: 58%

“…Alpha diversity was measured with the Chao1 (richness), Shannon diversity, and observed ASVs metrics (only observed ASV metrics are reported here for brevity). Beta diversity was evaluated with the phylogeny-based unweighted UniFrac (Park et al, 2019a) distance metric and visualized using Principal Coordinate Analysis (PCoA) plots. The F:B ratio was calculated as the ratio of the dominant phyla Firmicutes and Bacteroidetes.…”

Section: Methodsmentioning

confidence: 99%

“…Collectively, these results clearly show that the male rats had a worse stroke outcome as confirmed by their lower survival and greater sensory motor deficit as compared to age-matched female rats. is an estimate of health and an elevated F:B ratio is seen in aging and disease states such as metabolic syndrome (Natividad et al, 2018) and stroke (Park et al, 2019a, Spychala et al, 2018.…”

Section: Art As Response Variablementioning

confidence: 99%

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Sex Differences in Stroke Outcome Are Associated With Constitutive Gut Dysbiosis and Stroke-induced Gut Permeability

El-Hakim

Mani

Eldouh

et al. 2020

Preprint

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Background: Sex differences in experimental stroke are well documented, such that adult males show worse outcomes compared to adult females, including greater infarct volume, increased stroke-induced mortality and more severe sensory-motor impairment. Based on recent evidence that gut dysbiosis may be an early response to stroke, the present study tested the hypothesis that in the acute phase, stroke will result in greater permeability of the gut blood barrier and gut dysbiosis in males as compared to females. Method: Male and female Sprague Dawley rats (5-7 months of age) were subject to endothelin (ET)-1-induced middle cerebral artery occlusion (MCAo). Fecal samples, blood draws and sensory motor tests were conducted pre and 2d after MCAo. Fecal samples were analyzed for 16s sequencing and short chain fatty acids (SCFAs). Gut permeability was assessed in serum samples using biomarkers of gut permeability as well as functional assays using size-graded dextrans. Results: We confirmed stroke-induced sex differences, including greater mortality and sensory motor deficit in males as compared to age-matched female rats. Remarkably, fecal 16s sequencing showed greater bacterial diversity in females at baseline (prior to stroke) while 2 days after stroke, these measures were similar between the sexes. In contrast, fecal levels of short chain fatty acids (SCFAs) which are usually beneficial, were higher in males. MCAo-induced gut permeability was much worse in males as compared to females, as indicated by histological analysis, biochemical markers in serum, and serum measurement of fluorescent-labeled dextrans following oral gavage. Additionally, males had higher serum levels of proinflammatory cytokines IL-17A, MCP-1, IL-5 and EGF compared to females after stroke. Predictive modeling indicated that markers of gut permeability were associated with stroke-induced sensory-motor impairment. Conclusions: Poor stroke outcomes in adult males is mirrored by increased gut permeability in this group. Additionally, these data suggest that constitutive sex differences in the diversity and richness of gut microbial communities may predispose better functional outcomes after stroke in females, and support the idea that preventative modification of the gut microbiome may reduce the risk for stroke in vulnerable populations such as the elderly or those with co-morbid conditions.

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Section: Sex Differences In Bacterial Diversitysupporting

confidence: 94%

Section: Discussionmentioning

confidence: 58%

Section: Methodsmentioning

confidence: 99%

Section: Art As Response Variablementioning

confidence: 99%

See 2 more Smart Citations

Sex Differences in Stroke Outcome Are Associated With Constitutive Gut Dysbiosis and Stroke-induced Gut Permeability

El-Hakim

Mani

Eldouh

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…As the most abundant microorganism being interdependent with human hosts, the gut microbiota not only constitutes a specialized microecosystem in gastrointestinal (GI) tract and harmonizes their relations dynamically, but is engaged in metabolic regulation and immune defense through the interplay with multiple distant organs and systems beyond the intestine 9 . In recent years, extensive studies have revealed that the microbiota–gut–brain axis is closely implicated in the pathophysiology of neurological diseases, which include but are not limited to Alzheimer’s disease 10 , autism spectrum disorder 11 , stroke 12 , 13 , multiple sclerosis 14 , and Parkinson’s disease 15 , 16 . As a crucial part of the axis, intestinal barrier dysfunction played an essential role in both gastrointestinal inflammatory diseases and neuropathology as well 17 .…”

Section: Introductionmentioning

confidence: 99%

The alteration of gut microbiome and metabolism in amyotrophic lateral sclerosis patients

Zeng

Shen²,

Chen

et al. 2020

Sci Rep

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Direct arterial damage and neurovascular unit disruption by mechanical thrombectomy in a rat stroke model

Sasaki

Yamashita

Tadokoro

et al. 2020

J of Neuroscience Research

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Mechanical thrombectomy (MT) is a standard treatment for acute ischemic stroke that could cause hemorrhagic complications. We aimed to evaluate the pathology of MT‐induced arterial damage and neurovascular unit (NVU) disruption in relation to tissue‐type plasminogen activator (tPA) injection for acute ischemic stroke. We induced transient middle cerebral artery occlusion in male SHR/Izm rats for 2 hr. This was followed by reperfusion with/without tPA (3 mg/kg) and “rough suture” insertion that mimicked MT once or thrice (MT1 or MT3). Compared with the control group, the tPA + MT3 group presented with an increase in the cerebral infarct and hemorrhage with severer IgG leakage. Moreover, structural damage reaching the tunica media was detected in the MT3 and tPA + MT3 groups. The tPA + MT3 group presented with increased matrix metalloproteinase‐9 (MMP‐9) and vascular endothelial growth factor (VEGF) expression with some MMP9‐positive cells expressing a neutrophil marker myeloperoxidase. Furthermore, basal lamina detachment from astrocyte foot processes was observed in the tPA + MT1 and tPA + MT3 groups. These findings suggest that MT causes direct arterial damage, as well as VEGF and MMP9 upregulation, which results in NVU disruption and hemorrhagic complications in acute ischemic stroke, especially when combined with tPA.

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Reproductive Senescence and Ischemic Stroke Remodel the Gut Microbiome and Modulate the Effects of Estrogen Treatment in Female Rats

Cited by 45 publications

References 87 publications

Sex Differences in Stroke Outcome Are Associated With Constitutive Gut Dysbiosis and Stroke-induced Gut Permeability

Sex Differences in Stroke Outcome Are Associated With Constitutive Gut Dysbiosis and Stroke-induced Gut Permeability

The alteration of gut microbiome and metabolism in amyotrophic lateral sclerosis patients

Direct arterial damage and neurovascular unit disruption by mechanical thrombectomy in a rat stroke model

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