Microbiota Gut–Brain Axis in Ischemic Stroke: A Narrative Review with a Focus about the Relationship with Inflammatory Bowel Disease
TL;DR: In this article, a review of the role of the gut-brain microbiota axis in ischemic stroke and its potential role in the interaction between inflammatory bowel disease and stroke was presented.
Abstract: The gut microbiota is emerging as an important player in neurodevelopment and aging as well as in brain diseases including stroke, Alzheimer’s disease, and Parkinson’s disease. The complex interplay between gut microbiota and the brain, and vice versa, has recently become not only the focus of neuroscience, but also the starting point for research regarding many diseases such as inflammatory bowel diseases (IBD). The bi-directional interaction between gut microbiota and the brain is not completely understood. The aim of this review is to sum up the evidencesconcerningthe role of the gut–brain microbiota axis in ischemic stroke and to highlight the more recent evidences about the potential role of the gut–brain microbiota axis in the interaction between inflammatory bowel disease and ischemic stroke.
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TL;DR: In this article , the authors provide an overview of the normal composition of the gut microbiota, its functions, the mechanisms leading to dysbiosis, its consequences in an intensive care setting, and highlight the concept of the Gut-organ axis.
Abstract: Abstract Gut microbiota plays an essential role in health and disease. It is constantly evolving and in permanent communication with its host. The gut microbiota is increasingly seen as an organ, and its failure, reflected by dysbiosis, is seen as an organ failure associated with poor outcomes. Critically ill patients may have an altered gut microbiota, namely dysbiosis, with a severe reduction in “health-promoting” commensal intestinal bacteria (such as Firmicutes or Bacteroidetes) and an increase in potentially pathogenic bacteria (e.g. Proteobacteria). Many factors that occur in critically ill patients favour dysbiosis, such as medications or changes in nutrition patterns. Dysbiosis leads to several important effects, including changes in gut integrity and in the production of metabolites such as short-chain fatty acids and trimethylamine N-oxide. There is increasing evidence that gut microbiota and its alteration interact with other organs, highlighting the concept of the gut–organ axis. Thus, dysbiosis will affect other organs and could have an impact on the progression of critical diseases. Current knowledge is only a small part of what remains to be discovered. The precise role and contribution of the gut microbiota and its interactions with various organs is an intense and challenging research area that offers exciting opportunities for disease prevention, management and therapy, particularly in critical care where multi-organ failure is often the focus. This narrative review provides an overview of the normal composition of the gut microbiota, its functions, the mechanisms leading to dysbiosis, its consequences in an intensive care setting, and highlights the concept of the gut–organ axis.
20 citations
TL;DR: In this article , male and female mice received either male or female microbiota through FMT and established a model of ischemic stroke, which was triggered by MCAO (middle cerebral artery occlusion), and sham surgery served as a control.
Abstract: Abstract Background and purpose Stroke is associated with high disability and mortality rates and increases the incidence of organ-related complications. Research has revealed that the outcomes and prognosis of stroke are regulated by the state of the intestinal microbiota. However, the possibility that the manipulation of the intestinal microbiota can alter sex-related stroke outcomes remain unknown. Methods To verify the different effects of microbiota from different sexes on stroke outcomes, we performed mouse fecal microbiota transplantation (FMT) and established a model of ischemic stroke. Male and female mice received either male or female microbiota through FMT. Ischemic stroke was triggered by MCAO (middle cerebral artery occlusion), and sham surgery served as a control. Over the next few weeks, the mice underwent neurological evaluation and metabolite and inflammatory level detection, and we collected fecal samples for 16S ribosomal RNA analysis. Results We found that when the female mice were not treated with FMT, the microbiota (especially the Firmicutes-to-Bacteroidetes ratio) and the levels of three main metabolites tended to resemble those of male mice after experimental stroke, indicating that stroke can induce an ecological imbalance in the biological community. Through intragastric administration, the gut microbiota of male and female mice was altered to resemble that of the other sex. In general, in female mice after MCAO, the survival rate was increased, the infarct area was reduced, behavioral test performance was improved, the release of beneficial metabolites was promoted and the level of inflammation was mitigated. In contrast, mice that received male microbiota were much more hampered in terms of protection against brain damage and the recovery of neurological function. Conclusion A female-like biological community reduces the level of systemic proinflammatory cytokines after ischemic stroke. Poor stroke outcomes can be positively modulated following supplementation with female gut microbiota.
5 citations
TL;DR: This review addresses the question of how sepsis and stroke can dysregulate this adaptive response, notably by impairing the central integration of peripheral signaling, but also by efferent control of the immune response.
Abstract: Despite recent therapeutic advances, ischemic stroke is still a leading cause of death and disability. There is renewed attention on peripheral inflammatory signaling as a way of modulating the post-ischemic neuro-inflammatory process. The immune-brain crosstalk has long been the focus for understanding the mechanisms of sickness behavior, which is an adaptive autonomic, neuroendocrine, and behavioral response to a peripheral inflammation. It is mediated by humoral and neural pathways that mainly involve the circumventricular organs and vagal nerve, respectively. In this review we address the question of how sepsis and stroke can dysregulate this adaptive response, notably by impairing the central integration of peripheral signaling, but also by efferent control of the immune response. We highlight the potential role of gut–brain and brain–spleen signaling in stroke.
5 citations
TL;DR: In this article , the authors summarize the role of the microbiota-gut-brain axis (MGBA) in the occurrence and development of depression, especially the important role of MGBA in the mechanism of action of antidepressants.
Abstract: Depression is a common and severe mental disease that places a heavy burden on human society, which can lead to decreased cognitive function, energy loss, insomnia, and even suicide. Although medication plays an important role in improving the symptoms of depression, approximately one third of people with depression do not significantly benefit from medication and experience various adverse reactions. Recently, increasing evidence has shown that gut microbes play an important role in the occurrence and development of depression. There have been illuminating studies previously conducted on the relationship between antidepressant chemicals, traditional Chinese medicine, and the microbiota-gut-brain axis (MGBA). Therefore, in this review, we summarize the role of the MGBA in the occurrence and development of depression, especially the important role of the MGBA in the mechanism of action of antidepressants. Modulation of the MGBA is proposed to enhance the efficacy of antidepressant drugs and reduce their side effects and disease recurrence, so as to provide a new method for the treatment of depression.
3 citations
TL;DR: A review of the immune-related mechanisms of the gut-brain axis after stroke is presented in this article , where potential therapeutic targets for the future effective treatment of patients with ischemic stroke are discussed.
Abstract: After an ischemic stroke (IS) occurs, immune cells begin traveling to the brain and immune system from the gut and gastrointestinal tract, where most of them typically reside. Because the majority of the body’s macrophages and more than 70% of the total immune cell pool are typically found within the gut and gastrointestinal tract, inflammation and immune responses in the brain and immune organs require the mobilization of a large number of immune cells. The bidirectional communication pathway between the brain and gut is often referred to as the gut-brain axis. IS usually leads to intestinal motility disorders, dysbiosis of intestinal microbiota, and a leaky gut, which are often associated with poor prognosis in patients with IS. In recent years, several studies have suggested that intestinal inflammation and immune responses play key roles in the development of IS, and thus may become potential therapeutic targets that can drive new therapeutic strategies. However, research on gut inflammation and immune responses after stroke remains in its infancy. A better understanding of gut inflammation and immune responses after stroke may be important for developing effective therapies. This review discusses the immune-related mechanisms of the gut-brain axis after IS and compiles potential therapeutic targets to provide new ideas and strategies for the future effective treatment of IS.
2 citations
References
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TL;DR: It is determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis and mice deficient for the SCFA receptor FFAR2 mirroredmicroglia defects found under GF conditions, suggesting that host bacteria vitally regulate microglian maturation and function.
Abstract: As the tissue macrophages of the CNS, microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. We observed substantial contributions of the host microbiota to microglia homeostasis, as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype, leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features. We determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis. Accordingly, mice deficient for the SCFA receptor FFAR2 mirrored microglia defects found under GF conditions. These findings suggest that host bacteria vitally regulate microglia maturation and function, whereas microglia impairment can be rectified to some extent by complex microbiota.
2,096 citations
TL;DR: The high incidence for dysphagia and pneumonia is a consistent finding with stroke patients, and the pneumonia risk is greatest in stroke patients with aspiration.
Abstract: Objective— To determine the incidence of dysphagia and associated pulmonary compromise in stroke patients through a systematic review of the published literature. Methods— Databases were searched (1966 through May 2005) using terms “cerebrovascular disorders,” “deglutition disorders,” and limited to “humans” for original articles addressing the frequency of dysphagia or pneumonia. Data sources included Medline, Embase, Pascal, relevant Internet addresses, and extensive hand searching of bibliographies of identified articles. Selected articles were reviewed for quality, diagnostic methods, and patient characteristics. Comparisons were made of reported dysphagia and pneumonia frequencies. The relative risks (RRs) of developing pneumonia were calculated in patients with dysphagia and confirmed aspiration. Results— Of the 277 sources identified, 104 were original, peer-reviewed articles that focused on adult stroke patients with dysphagia. Of these, 24 articles met inclusion criteria and were evaluated. The r...
1,573 citations
TL;DR: Functional genomic, biochemical, and physiologic studies reveal that Gpr41 is a regulator of host energy balance through effects that are dependent upon the gut microbiota.
Abstract: The distal human intestine harbors trillions of microbes that allow us to extract calories from otherwise indigestible dietary polysaccharides. The products of polysaccharide fermentation include short-chain fatty acids that are ligands for Gpr41, a G protein-coupled receptor expressed by a subset of enteroendocrine cells in the gut epithelium. To examine the contribution of Gpr41 to energy balance, we compared Gpr41-/- and Gpr41+/+ mice that were either conventionally-raised with a complete gut microbiota or were reared germ-free and then cocolonized as young adults with two prominent members of the human distal gut microbial community: the saccharolytic bacterium, Bacteroides thetaiotaomicron and the methanogenic archaeon, Methanobrevibacter smithii. Both conventionally-raised and gnotobiotic Gpr41-/- mice colonized with the model fermentative community are significantly leaner and weigh less than their WT (+/+) littermates, despite similar levels of chow consumption. These differences are not evident when germ-free WT and germ-free Gpr41 knockout animals are compared. Functional genomic, biochemical, and physiologic studies of germ-free and cocolonized Gpr41-/- and +/+ littermates disclosed that Gpr41-deficiency is associated with reduced expression of PYY, an enteroendocrine cell-derived hormone that normally inhibits gut motility, increased intestinal transit rate, and reduced harvest of energy (short-chain fatty acids) from the diet. These results reveal that Gpr41 is a regulator of host energy balance through effects that are dependent upon the gut microbiota.
1,360 citations
TL;DR: It is demonstrated through 13C high-resolution magic-angle-spinning that 13C acetate from fermentation of 13C-labelled carbohydrate in the colon increases hypothalamic 13Cacetate above baseline levels, suggesting that acetate has a direct role in central appetite regulation.
Abstract: Increased intake of dietary carbohydrate that is fermented in the colon by the microbiota has been reported to decrease body weight, although the mechanism remains unclear. Here we use in vivo11C-acetate and PET-CT scanning to show that colonic acetate crosses the blood–brain barrier and is taken up by the brain. Intraperitoneal acetate results in appetite suppression and hypothalamic neuronal activation patterning. We also show that acetate administration is associated with activation of acetyl-CoA carboxylase and changes in the expression profiles of regulatory neuropeptides that favour appetite suppression. Furthermore, we demonstrate through 13C high-resolution magic-angle-spinning that 13C acetate from fermentation of 13C-labelled carbohydrate in the colon increases hypothalamic 13C acetate above baseline levels. Hypothalamic 13C acetate regionally increases the 13C labelling of the glutamate–glutamine and GABA neuroglial cycles, with hypothalamic 13C lactate reaching higher levels than the ‘remaining brain’. These observations suggest that acetate has a direct role in central appetite regulation.
1,058 citations
TL;DR: It is demonstrated that high blood pressure is associated with gut microbiota dysbiosis, both in animal and human hypertension, and dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension.
Abstract: Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis This study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension because genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure Bacterial DNA from fecal samples of 2 rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes/Bacteroidetes ratio These changes were accompanied by decreases in acetate- and butyrate-producing bacteria In addition, the microbiota of a small cohort of human hypertensive patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes/Bacteroidetes ratio In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes/Bacteroidetes ratio These observations demonstrate that high blood pressure is associated with gut microbiota dysbiosis, both in animal and human hypertension They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension
988 citations