The Influence of Gut Dysbiosis in the Pathogenesis and Management of Ischemic Stroke

Abstract

Recent research on the gut microbiome has revealed the influence of gut microbiota (GM) on ischemic stroke pathogenesis and treatment outcomes. Alterations in the diversity, abundance, and functions of the gut microbiome, termed gut dysbiosis, results in dysregulated gut–brain signaling, which induces intestinal barrier changes, endotoxemia, systemic inflammation, and infection, affecting post-stroke outcomes. Gut–brain interactions are bidirectional, and the signals from the gut to the brain are mediated by microbially derived metabolites, such as trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs); bacterial components, such as lipopolysaccharide (LPS); immune cells, such as T helper cells; and bacterial translocation via hormonal, immune, and neural pathways. Ischemic stroke affects gut microbial composition via neural and hypothalamic–pituitary–adrenal (HPA) pathways, which can contribute to post-stroke outcomes. Experimental and clinical studies have demonstrated that the restoration of the gut microbiome usually improves stroke treatment outcomes by regulating metabolic, immune, and inflammatory responses via the gut–brain axis (GBA). Therefore, restoring healthy microbial ecology in the gut may be a key therapeutic target for the effective management and treatment of ischemic stroke.

Ischemic Brain Neurodegeneration

“…Stroke is divided into two categories: ischemic and hemorrhagic. Ischemic stroke accounts for approximately 70–85% of all cases [ 5 , 6 ]. Clinically, stroke is defined as local damage to the parenchyma of the brain caused by a lack of blood supply by occlusion or narrowing of an artery to a specific region, resulting in the death of neurons [ 5 ].…”

“…Ischemic stroke accounts for approximately 70–85% of all cases [ 5 , 6 ]. Clinically, stroke is defined as local damage to the parenchyma of the brain caused by a lack of blood supply by occlusion or narrowing of an artery to a specific region, resulting in the death of neurons [ 5 ]. Ischemic stroke is a huge and growing health challenge in the modern world [ 7 ].…”

“…Of the population of one million a year, 2400 will suffer a stroke, and a year later about 50% will be independent [ 9 , 10 ]. It is currently estimated that the number of post-ischemic patients worldwide is around 33 million with 6 million deaths, and another 5 million remain permanently disabled, putting a heavy economic burden on the family and society [ 5 , 7 , 8 , 9 , 11 ]. According to the forecast, the number of patients after ischemic stroke in the world will increase to 77 million in 2030 [ 9 , 11 ].…”

“…Several studies have confirmed that the dynamics of the gut microbiome can be adjusted towards a healthy state by restoring a favorable microbial population and elevated butyric acid levels. In stroke cases, supplements rich in short-chain fatty acid-producing bacteria have been shown to significantly reduce gut leakage and inflammation; pathogenic bacteria (e.g., Bacteroides , Klebsiella, and Haemophilus ) should be reduced, and increase the population of beneficial bacteria (e.g., Lactobacillus, Butyricicoccus, and Meganonas ), which in turn inhibit neuronal cell apoptosis, oxidative stress and lead to the prevention of neurobehavioral abnormalities [ 5 , 15 , 19 ]. In summary, short-chain fatty acid producing bacteria and butyric acid supplementation have proven to be an effective treatment for stroke, although additional large-scale randomized clinical trials are needed in the future to demonstrate the efficacy and safety of short-chain fatty acids in treating patients with complications after stroke [ 5 , 15 , 19 ].…”

“…In stroke cases, supplements rich in short-chain fatty acid-producing bacteria have been shown to significantly reduce gut leakage and inflammation; pathogenic bacteria (e.g., Bacteroides , Klebsiella, and Haemophilus ) should be reduced, and increase the population of beneficial bacteria (e.g., Lactobacillus, Butyricicoccus, and Meganonas ), which in turn inhibit neuronal cell apoptosis, oxidative stress and lead to the prevention of neurobehavioral abnormalities [ 5 , 15 , 19 ]. In summary, short-chain fatty acid producing bacteria and butyric acid supplementation have proven to be an effective treatment for stroke, although additional large-scale randomized clinical trials are needed in the future to demonstrate the efficacy and safety of short-chain fatty acids in treating patients with complications after stroke [ 5 , 15 , 19 ]. It is essential to identify conservative and reliable biomarkers of the gut microbiome to assist in the development of next-generation microbiome-based therapeutic agents for the prevention of stroke and post-stroke neurobehavioral deficits or dementia, as well as monitoring disease progression and therapeutic efficacy.…”