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Brain-gut communication and potential applications of microecological treatments in stroke
Abstract
Stroke is a cerebrovascular disease with high incidence rates, serious disability and increased mortality rates, thereby posing a serious threat to human health. The mechanisms of brain-gut communication have gradually emerged in recent times. This article focuses on the gut-brain axis and discusses the bidirectional regulatory pathways between gut microecology and stroke via the neurotransmitter, colony metabolite, endocrine, and immunoregulatory pathways. Additionally, it summarizes the latest applications of gut microecological agents in stroke, which may provide new research ideas and clinical treatment strategies for the microecological diagnosis and therapy of stroke.
1 Introduction
As one of the leading causes of mortality and lifelong disability globally, stroke imposes significant economic, social and clinical burdens on patients, families and health services (GBD 2019 Stroke Collaborators, 2021; Kim et al., 2020). Particularly in low and middle income countries, stroke incidence continues to increase as a result of progressive global population aging and rise in the prevalence of cardiovascular risk factors, namely obesity, dyslipidemia, hypertension and diabetes mellitus (O'Donnell et al., 2016; Vaduganathan et al., 2022). The functional recovery post-stroke is often incomplete since there are limited effective treatment options for the condition despite advances in acute reperfusion therapies, such as mechanical thrombectomy and thrombolysis (Campbell and Khatri, 2020). To improve prevention, treatment and prognosis of stroke, identification of novel pathophysiological mechanisms and pharmacological targets are increasing demanded.
The role of gut microbiota in causing neurological diseases has gained increased attention in recent times. Gut microbiota collectively refers to a complex and dynamic microbial system, which is harbored in the human and is composed of archaea, fungi, viruses and bacteria (Sender et al., 2016). In view of their huge genetic repertoire, these microorganisms have been found to participate in physiological processes, such as maintenance of intestinal barrier integrity, maturation of immune system, protection against pathogenic invasion, synthesis of vitamins, and metabolism of nutrients (Sommer and Bäckhed, 2013; Round and Mazmanian, 2009). Various diseases such as cardiovascular diseases (CVDs), central nervous system (CNS) disorders, immune-mediated conditions and metabolic disorders developed as a result of dysbiosis (imbalance of gut microbiome) (Lynch and Pedersen, 2016; Tilg et al., 2020).
The gastrointestinal tract (GIT) is linked to the CNS by a two-way directional communication network known as gut-brain axis (GBA) via immune, metabolic and neural pathways (Cryan and Dinan, 2012). The development, function and behavior of the brain can be influenced by gut microbiota through this axis with the brain modulating the mobility, secretion, permeability and immune responses of the gut (Carabotti et al., 2015). Growing evidence suggests that the potential for gut microbiota-derived hormones, inflammatory mediators, neurotransmitters and metabolites to cross the barrier of intestines and occasionally the blood–brain barrier (BBB) can directly or indirectly affect neuroinflammatory processes and neuronal activity (Sharon et al., 2016; Fung et al., 2017). Acute brain injuries including stroke, neuropsychiatric conditions and neurogenerative disorders have been linked with GBA dysregulation (Sampson and Mazmanian, 2015; Dinan and Cryan, 2020; Góralczyk-Bińkowska et al., 2022).
Through emerging studies, scientists have discovered stroke as a systemic disease and focal cerebrovascular event that significantly impact function of gut and composition of microbiome (Chidambaram et al., 2022; Szegedi et al., 2025). Also, secondary brain function, systemic inflammation and immune dysfunction were exacerbated by acute cerebral ischemia or hemorrhage-induced intestinal dysmotility, increased permeability of gut and microbiota dysbiosis (Singh et al., 2016; Winek et al., 2016). In contrast, susceptibility and recovery of stroke, infarct size, and inflammation after stroke are influenced by pre-existing composition of gut microbiota and their metabolites (Benakis et al., 2016; Yamashiro et al., 2017). Based on available evidence, gut microbiota can be considered as a contributor to pathogenesis of stroke and as a potential target for treatment of the condition.
In this context, scientists have given much attention to microecological agents (MEAs), namely microbiota-derived metabolites, synbiotics, prebiotics and probiotics, which have been regarded as adjunctive schemes for prevention, treatment and rehabilitation of stroke (Zhong et al., 2021; Li et al., 2023). It is evidenced that the aforementioned interventions may regulate metabolic pathways, reduce neuroinflammation, ameliorate homeostasis of immune system and promote post-stroke recovery of neurons by modulating of composition and function of gut microbiome (Sadler et al., 2020). Nevertheless, scientists have not clearly understood the mechanisms that underlie interaction of microbiota–brain in stroke, while further systematic evaluation of clinical translation of microbiome-based therapies is required.
This article explores four major regulatory pathways and mechanisms involved in brain-gut communication based on the concept of the GBA (Figure 1). It also summarizes the cutting-edge applications of MEAs in the diagnosis and treatment of stroke (Table 1), thus providing new research ideas and clinical treatment approaches for microecological diagnosis and stroke treatment.
Four major regulatory pathways of brain-gut dialogues.
Table 1
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