Examining the Role of the Microbiota-Gut-Brain Axis in Stroke.
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ABSTRACT:
SUBMITTER: Durgan DJ
PROVIDER: S-EPMC6646086 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
Publications
Examining the Role of the Microbiota-Gut-Brain Axis in Stroke.
Durgan David J DJ Lee Juneyoung J McCullough Louise D LD Bryan Robert M RM
Stroke 20190705 8
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Project description:The gut-brain axis is increasingly recognized as an important pathway of communication and of physiological regulation, and gut microbiota seems to play a significant role in this mutual relationship. Oxidative stress is one of the most important pathogenic mechanisms for both neurodegenerative diseases, such as Alzheimer's or Parkinson's, and acute conditions, such as stroke or traumatic brain injury. A peculiar microbiota type might increase brain inflammation and reactive oxygen species levels and might favor abnormal aggregation of proteins. Reversely, brain lesions of various etiologies result in alteration of gut properties and microbiota. These recent hypotheses could open a door for new therapeutic approaches in various neurological diseases.
| S-EPMC6304899 | biostudies-other
Project description:Emerging evidence suggests that gut-brain-microbiota axis (GBMAx) may play a pivotal role linking gastrointestinal and neuronal disease. In this review, we summarize the latest advances in studies of GBMAx in inflammatory bowel disease (IBD) and ischemic stroke. A more thorough understanding of the GBMAx could advance our knowledge about the pathophysiology of IBD and ischemic stroke and help to identify novel therapeutic targets via modulation of the GBMAx.
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Project description:Gut microbiota play an important role in maintaining intestinal health and are involved in the metabolism of carbohydrates, lipids, and amino acids. Recent studies have shown that the central nervous system (CNS) and enteric nervous system (ENS) can interact with gut microbiota to regulate nutrient metabolism. The vagal nerve system communicates between the CNS and ENS to control gastrointestinal tract functions and feeding behavior. Vagal afferent neurons also express receptors for gut peptides that are secreted from enteroendocrine cells (EECs), such as cholecystokinin (CCK), ghrelin, leptin, peptide tyrosine tyrosine (PYY), glucagon-like peptide-1 (GLP-1), and 5-hydroxytryptamine (5-HT; serotonin). Gut microbiota can regulate levels of these gut peptides to influence the vagal afferent pathway and thus regulate intestinal metabolism via the microbiota-gut-brain axis. In addition, bile acids, short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and Immunoglobulin A (IgA) can also exert metabolic control through the microbiota-gut-liver axis. This review is mainly focused on the role of gut microbiota in neuroendocrine regulation of nutrient metabolism via the microbiota-gut-brain-liver axis.
| S-EPMC7232453 | biostudies-literature
Project description:Disturbances along the brain-gut-microbiota axis may significantly contribute to the pathogenesis of neurodegenerative disorders. Alzheimer's disease (AD) is the most frequent cause of dementia characterized by a progressive decline in cognitive function associated with the formation of amyloid beta (A?) plaques and neurofibrillary tangles. Alterations in the gut microbiota composition induce increased permeability of the gut barrier and immune activation leading to systemic inflammation, which in turn may impair the blood-brain barrier and promote neuroinflammation, neural injury, and ultimately neurodegeneration. Recently, A? has also been recognized as an antimicrobial peptide participating in the innate immune response. However, in the dysregulated state, A? may reveal harmful properties. Importantly, bacterial amyloids through molecular mimicry may elicit cross-seeding of misfolding and induce microglial priming. The A? seeding and propagation may occur at different levels of the brain-gut-microbiota axis. The potential mechanisms of amyloid spreading include neuron-to-neuron or distal neuron spreading, direct blood-brain barrier crossing or via other cells as astrocytes, fibroblasts, microglia, and immune system cells. A growing body of experimental and clinical data confirms a key role of gut dysbiosis and gut microbiota-host interactions in neurodegeneration. The convergence of gut-derived inflammatory response together with aging and poor diet in the elderly contribute to the pathogenesis of AD. Modification of the gut microbiota composition by food-based therapy or by probiotic supplementation may create new preventive and therapeutic options in AD.
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Project description:BackgroundHyperuricemia is considered as an independent risk factor for acute ischemic stroke (AIS), and some AIS patients are accompanied by an increase in serum uric acid. Recent studies have highlighted the important role of gut microbiota in both hyperuricemia and AIS, but there is little available data on the relationship between gut microbiota and the pathogenesis of AIS with hyperuricemia (HAS).MethodsHere we profiled the gut microbiota composition in 63 HAS patients and 269 non-HAS patients through 16s rRNA sequencing. Male rat with hyperuricemia were subjected to middle cerebral artery occlusion (MCAO) to establish HAS model and were then treated with Parabacteroides distasonis. Subsequently, the neurological deficit, pathological damages and blood-brain barrier disruption were evaluated. Moreover, the levels of ROS, inflammatory cytokines, NF-𝜿B pathway related protein, and vascular density markers were determined.ResultsThere were significant differences of gut microbiota composition between HAS patients and non-HAS patients, and a significant decrease in the abundance of Parabacteroides in HAS patients compared to non-HAS patients. Animal experiments showed that supplementation with P. distasonis increased beneficial commensal bacteria, significantly improved neurological deficits, pathological damages and BBB disruption, as well as reduced the level of serum uric acid in HAS rats. We further demonstrated that P. distasonis treatment decreased ROS level and increased SOD2 level, thereby reducing oxidative stress. Meanwhile, P. distasonis effectively inhibited NF-𝜿B signal pathway and reduced the production of inflammatory cytokines, including TNF-α and IL-1β, alleviating the inflammatory response. Notably, P. distasonis treatment increased the levels of vascular density markers including cluster of differentiation 31 (CD31) and alpha-smooth muscle actin (α-SMA), ameliorating vascular damage in HAS rats.ConclusionsTogether, these findings highlighted the important role of P. distasonis in the pathogenesis of HAS, and its mechanism was involved in the regulation of gut microbiota-gut-brain axis, which implied a novel strategy against HAS.
| S-EPMC11539330 | biostudies-literature
Project description:BackgroundThe complexity of the pathogenic mechanisms underlying neurodegenerative disorders such as Parkinson's disease (PD) is attributable to multifactorial changes occurring at a molecular level, influenced by genetics and environmental interactions. However, what causes the main hallmarks of PD is not well understood. Recent data increasingly suggest that imbalances in the gut microbiome composition might trigger and/or exacerbate the progression of PD.ObjectiveThe present review aims to (1) report emerging literature showing changes in microbiota composition of PD patients compared to healthy individuals and (2) discuss how these changes may initiate and/or perpetuate PD pathology.MethodsWe analyzed 13 studies published from 2015 and included in this review. Altered microbial taxa were compiled in a detailed table summarizing bacterial changes in fecal/mucosal samples. The methodology was systematically reviewed across the articles and was also included in a table to facilitate comparisons between studies.ResultsMultiple studies found a reduction in short-chain fatty-acid-producing bacteria that can rescue neuronal damage through epigenetic mechanisms. Overall, the studies showed that changes in the gut microbiota composition might influence colonic inflammation, gut permeability, and α-synuclein aggregation, contributing to the neurogenerative process.ConclusionFurther studies with larger cohorts and high-resolution sequencing methods are required to better define gut microbiota changes in PD. Furthermore, additional longitudinal studies are required to determine the causal link between these changes and PD pathogenesis as well as to study the potential of the intestinal microbiota as a biomarker.
| S-EPMC6856467 | biostudies-literature
Project description:AimsThe purpose of this review is to explore the interconnected pathways of the microbiota-gut-brain axis (MGBA), focusing on the roles of the vagus nerve and glucagon like peptide-1 in appetite control, and in the development of obesity and diabetes.MethodsType 2 diabetes mellitus (T2DM) and obesity are metabolic disorders whose prevalence has significantly increased in recent decades and is expected to increase every year, to pandemic proportions. These two pathologies often coexist and have substantial public health implications. The term "diabesity" defines the pathophysiological connection between overweight and T2DM. The gut microbiota affects many aspects of the host. Beyond the regulation of intestinal functions and the activation of immune responses, the gut microbiota plays a role in central nervous system functions (i.e., mood, and psychiatric conditions associated with stress and memory) and is a central regulator of metabolism and appetite.ResultsThe MGBA involves pathways such as the autonomic and enteric nervous systems, the hypothalamic- pituitary-adrenal axis, the immune system, enteroendocrine cells, and microbial metabolites. Notably, the vagus nerve plays an essential role in eating behavior by modulating appetite and learning nutritional preferences.ConclusionsBecause of its enteroendocrine cell-mediated interaction with the gut microbiota, the vagus nerve may provide a potential pathway through which gut microorganisms influence host feeding behavior and metabolic control of physiological and pathological conditions.
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Project description:BackgroundIschemic stroke belongs to "apoplexy" and its pathogenesis is characterized by qi deficiency and blood stasis combining with phlegm-damp clouding orifices. Buqi-Huoxue-Tongnao decoction (BHTD) is a traditional Chinese medicine formula for qi deficiency, blood stasis and phlegm obstruction syndrome. However, its efficacy and potential mechanism on ischemic stroke are still unclear. This study aims to investigate the protective effect and potential mechanism of BHTD against ischemic stroke.Materials and methodsMiddle cerebral artery occlusion (MCAO) surgery was carried out to establish an ischemic stroke model in rats. Subsequently, the rats were gavaged with different doses of BHTD (2.59, 5.175, 10.35 g/kg) for 14 days. The protective effects of BHTD on the brain and gut were evaluated by neurological function scores, cerebral infarction area, levels of brain injury markers (S-100B, NGB), indicators of gut permeability (FD-4) and bacterial translocation (DAO, LPS, D-lactate), and tight junction proteins (Occludin, Claudin-1, ZO-1) in brain and colon. 16S rRNA gene sequencing and metabolomic analysis were utilized to analyze the effects on gut microecology and screen for marker metabolites to explore potential mechanisms of BHTD protection against ischemic stroke.ResultsBHTD could effectively mitigate brain impairment, including reducing neurological damage, decreasing cerebral infarction and repairing the blood-brain barrier, and BHTD showed the best effect at the dose of 10.35 g/kg. Moreover, BHTD reversed gut injury induced by ischemic stroke, as evidenced by decreased intestinal permeability, reduced intestinal bacterial translocation, and enhanced intestinal barrier integrity. In addition, BHTD rescued gut microbiota dysbiosis by increasing the abundance of beneficial bacteria, including Turicibacter and Faecalibaculum. Transplantation of the gut microbiota remodeled by BHTD into ischemic stroke rats recapitulated the protective effects of BHTD. Especially, BHTD upregulated tryptophan metabolism, which promoted gut microbiota to produce more indole lactic acid (ILA). Notably, supplementation with ILA by gavage could alleviate stroke injury, which suggested that driving the production of ILA in the gut might be a novel treatment for ischemic stroke.ConclusionBHTD could increase gut microbiota-derived indole lactic acid to attenuate ischemic stroke via the gut-brain axis. Our current finding provides evidence that traditional Chinese medicine can ameliorate central diseases through regulating the gut microbiology.
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Project description:: The human gut hosts a wide and diverse ecosystem of microorganisms termed the microbiota, which line the walls of the digestive tract and colon where they co-metabolize digestible and indigestible food to contribute a plethora of biochemical compounds with diverse biological functions. The influence gut microbes have on neurological processes is largely yet unexplored. However, recent data regarding the so-called leaky gut, leaky brain syndrome suggests a potential link between the gut microbiota, inflammation and host co-metabolism that may affect neuropathology both locally and distally from sites where microorganisms are found. The focus of this manuscript is to draw connection between the microbiota-gut-brain (MGB) axis, antibiotics and the use of "BUGS AS DRUGS" for neurodegenerative diseases, their treatment, diagnoses and management and to compare the effect of current and past pharmaceuticals and antibiotics for alternative mechanisms of action for brain and neuronal disorders, such as Alzheimer disease (AD), Amyotrophic Lateral Sclerosis (ALS), mood disorders, schizophrenia, autism spectrum disorders and others. It is a paradigm shift to suggest these diseases can be largely affected by unknown aspects of the microbiota. Therefore, a future exists for applying microbial, chemobiotic and chemotherapeutic approaches to enhance translational and personalized medical outcomes. Microbial modifying applications, such as CRISPR technology and recombinant DNA technology, among others, echo a theme in shifting paradigms, which involve the gut microbiota (GM) and mycobiota and will lead to potential gut-driven treatments for refractory neurologic diseases.
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Project description:The gut microbiota plays an important role in regulating brain function, influencing psychological and emotional stability. The correlations between conspecific aggression, gut microbiota, and physiological homeostasis were further studied in inbred laying chicken lines, 63 and 72, which were diversely selected for Marek’s disease, and they also behave differently in aggression. Ten sixty-week-old hens from each line were sampled for blood, brain, and cecal content. Neurotransmitters, cytokines, corticosterone, and heterophil/lymphocyte ratios were determined. Cecal microbiota compositions were determined by bacterial 16s rRNA sequencing, and functional predictions were performed. Our data showed that the central serotonin and tryptophan levels were higher in line 63 compared to line 72 (p < 0.05). Plasma corticosterone, heterophil/lymphocyte ratios, and central norepinephrine were lower in line 63 (p < 0.05). The level of tumor necrosis factor α tended to be higher in line 63. Faecalibacterium, Oscillibacter, Butyricicoccus, and Bacteriodes were enriched in line 63 birds, while Clostridiales vadin BB60, Alistipes, Mollicutes RF39 were dominated in line 72. From the predicted bacterial functional genes, the kynurenine pathway was upregulated in line 72. These results suggested a functional linkage of the line differences in serotonergic activity, stress response, innate immunity, and gut microbiota populations.
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