Abstract
The microbiota–gut–brain axis (MGBA) is a bidirectional signaling pathway mediating the interaction of the microbiota, the intestine, and the central nervous system. While the MGBA plays a pivotal role in normal development and physiology of the nervous and gastrointestinal system of the host, its dysfunction has been strongly implicated in neurological disorders, where intestinal dysbiosis and derived metabolites cause barrier permeability defects and elicit local inflammation of the gastrointestinal tract, concomitant with increased pro-inflammatory cytokines, mobilization and infiltration of immune cells into the brain, and the dysregulated activation of the vagus nerve, culminating in neuroinflammation and neuronal dysfunction of the brain and behavioral abnormalities. In this topical review, we summarize recent findings in human and animal models regarding the roles of the MGBA in physiological and neuropathological conditions, and discuss the molecular, genetic, and neurobehavioral characteristics of zebrafish as an animal model to study the MGBA. The exploitation of zebrafish as an amenable genetic model combined with in vivo imaging capabilities and gnotobiotic approaches at the whole organism level may reveal novel mechanistic insights into microbiota–gut–brain interactions, especially in the context of neurological disorders such as autism spectrum disorder and Alzheimer’s disease.
Highlights
The microbiota–gut–brain axis (MGBA) is a bidirectional signaling cascade in which efferent signaling pathways originating from the central nervous system (CNS) regulate the activities of the intestine and the microbiota, while afferent signaling originating from the microbiota and the intestines affects the development and the function of the CNS [1]
The actions of the MGBA are known to be mediated by metabolites and cytokines that are generated by members of the gut microbiota or released from immune cells and intestinal cells activated by them, or by the streamlined direct connections between the brainstem and intestines via the vagus nerve [4]
We summarize recent human and other animal model findings regarding the MGBA and discuss the characteristics and utility of using zebrafish as an animal model to study the MGBA
Summary
The microbiota–gut–brain axis (MGBA) is a bidirectional signaling cascade in which efferent signaling pathways originating from the central nervous system (CNS) regulate the activities of the intestine and the microbiota, while afferent signaling originating from the microbiota and the intestines affects the development and the function of the CNS [1]. Imbalances of the gut microbiota, referred to as dysbiosis, and any associated malfunctions of the MGBA have been implicated in a variety of neurodevelopmental, neuropsychological, and neurodegenerative diseases These dysbiotic malfunctions have been closely associated with aberrant systemic inflammatory responses and have been shown to culminate in the brain defects that lead to behavioral defects and neuronal dysfunctions [5]. A more detailed understanding of the underlying mechanisms and physiological roles of the MGBA in the etiopathology in diseases will help to design novel therapeutics based on modulating MGBA activities. For these purposes, the zebrafish has emerged as an excellent animal model system to address the host–microbe interactions for both normal physiology and pathogenesis in vivo.
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