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The communication mechanism of the gut-brain axis and its effect on central nervous system diseases: A systematic review
Keywords
1. Introduction
Gut microbiota was discovered in the 19th century [1], and research thereinto evolved from the isolation and cultivation stage to the 16 s rRNA gene sequencing stage, and gradually developed towards the combination of culturomics and metagenomics approaches [2], [3]. In the late 20th and early 21st centuries, research into gut microbiota was mainly focused on the overall effect of probiotics and prebiotics on gut microbes, with a focus on the intervention effects of probiotics, mainly bifidobacterial and lactobacilli, on allergic diseases [4], [5]. Studies also explored the colonization of the maternal-infant gut microbiota and how factors like age, diet, and medication affect it [6]. The ongoing investigation into gut microbiota has sparked inquiries about the communication between the microbiome and the host, as well as the precise influence on the host's physiological processes. In recent times, researchers have utilized germ-free animals, animals with controlled microbial communities, and animals with transplanted microbiota to explore the effect of gut microbiota on host metabolic enzymes, intestinal epithelial barriers, gut endocrine signaling, and overall gut homeostasis [7], [8], [9], [10]. The gut microbiota regulates multiple metabolic pathways of the host, communicates with the host's metabolism, and forms a functionally connected gut-organ axis [11], [12], [13].
The effect of gut microbiota on the central nervous system (CNS) is significant. An increasing number of preclinical studies has proven the existence of bidirectional signal transduction between the brain and gut microbiome, involving mechanisms like the gut-brain communication, immunologic barrier, and neuroendocrine signal transduction [14]. As a complex microbial ecosystem existing in the digestive system of organisms, gut microbiota is colonized with maternal heredity at birth and changes due to dietary habits and environmental signals [15], [16]. In the presence of internal homeostasis, the gut microbiota supports its own survival and aids in regulating the host's normal physiological processes through the production of various small molecules and metabolites [17]. Alterations in the gut microbiota, including a rise in pathogenic bacteria and a decline in symbiotic bacteria, can lead to dysbiosis of the gut microbiota. This can trigger the production of metabolites and disrupt normal physiological and biochemical processes, leading to pathological changes in the host [18], [19], [20], [21]. The physiology and neurochemistry of the CNS in germ-free animals, or those treated with broad-spectrum antibiotics, differ from those of traditional animals [22]. This suggests that brain neurochemistry is influenced by specific gut microbiota [23], [24] and has led to increased research on "gut-microbiota-metabolite neuroscience" [25], [26]. The gut-brain axis (GBA) is receiving increased attention among neuroscientists. Changes in the microbiota lead to alterations in metabolites, cytokines, neurotransmitters, and glial cells [27], [28], [29]. These changes can affect neurodevelopmental abnormalities and substantial lesions, and have widespread effects on emotions, cognition, and behaviour [30], [31], [32], [33].
In the following, we first describe three communication pathways (neural pathway, immune pathway and neuroendocrine pathway) in GBA communication. These pathways serve as the main physiological channels between the brain and the gut. Through these three channels, the gut communicates with the brain in three ways: releasing active substances, quorum sensing, and secondary metabolites. Significant communication signals in GBA communication have been extensively discussed, encompassing the physiological intricacies of GBA communication and its correlation with studies on neurological disorders. Finally, we discuss the susceptibility factors of neurological disorders caused by GBA communication disorders and the latest treatment strategies. This research can serve as a valuable guide for readers interested in understanding the latest research on the impact of brain-gut axis interactions on the central nervous system. It aims to explore new therapeutic targets and strategies to delay the onset and progression of central nervous system diseases.
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