Abstract
Understanding how gut flora influences gut-brain communications has been the subject of significant research over the past decade. The broadening of the term “microbiota-gut-brain axis” from “gut-brain axis” underscores a bidirectional communication system between the gut and the brain. The microbiota-gut-brain axis involves metabolic, endocrine, neural, and immune pathways which are crucial for the maintenance of brain homeostasis. Alterations in the composition of gut microbiota are associated with multiple neuropsychiatric disorders. Although a causal relationship between gut dysbiosis and neural dysfunction remains elusive, emerging evidence indicates that gut dysbiosis may promote amyloid-beta aggregation, neuroinflammation, oxidative stress, and insulin resistance in the pathogenesis of Alzheimer’s disease (AD). Illustration of the mechanisms underlying the regulation by gut microbiota may pave the way for developing novel therapeutic strategies for AD. In this narrative review, we provide an overview of gut microbiota and their dysregulation in the pathogenesis of AD. Novel insights into the modification of gut microbiota composition as a preventive or therapeutic approach for AD are highlighted.
Highlights
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder of the central nervous system (CNS) characteristic of gradual cognitive decline [1]
3 Department of Life Sciences, National Natural Science Foundation of China, Shuangqing Road 83, Beijing 100085, China dissect the mechanisms underlying the pathogenesis of AD and to seek disease-modifying therapies (Fig. 1). Since it was first proposed by Hardy and Higgins in 1992, the amyloid cascade hypothesis has been the dominant theory of AD pathogenesis which holds that the accumulation of Aβ peptides derived from amyloid precursor protein (APP) is the initial event of AD pathogenesis [3]
The microbiota-gut-brain axis links gut microbiota and the brain via metabolic, endocrine, neural, and immune pathways that are crucial for the maintenance of brain homeostasis
Summary
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder of the central nervous system (CNS) characteristic of gradual cognitive decline [1]. The microbiota-gut-brain axis has emerged as a focal point of biomedical research and a potential therapeutic target for the treatment of CNS disorders [16, 17]. Albeit nascent in terms of the delineation of the mode of communication between gut microbiota and the brain, research using germ-free (GF) mice, antibiotic treatments, and prebiotic/probiotic complementation has provided persuasive evidence for several major potential pathways underlying the two-way communications between the GI tract and the CNS. SCFAs, which mainly consist of acetate, propionate, and butyrate, function through either G protein coupled receptors or histone deacetylases [46, 47] Such microbial products are active mediators of gut-brain communication and may serve as potential therapeutic targets for neurodevelopmental and neurodegenerative disorders. As a vast variety of chemical and mechanosensitive receptors are expressed on vagal afferents, and due to their role in interoceptive awareness, they respond to a variety of mechanical, chemical, and hormonal stimuli from gut microbiota and transfer gut
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