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      The role of short-chain fatty acids in central nervous system diseases: A bibliometric and visualized analysis with future directions

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          Abstract

          Background

          Short-chain fatty acids (SCFAs) are thought to play a key role in the microbe-gut-brain axis and involve in the pathogenesis of a variety of neurological diseases. This study aimed to identify research hotspots and evolution trends in SCFAs in central nervous diseases (CNS) and examine current research trends.

          Methods

          The bibliometric analysis was performed using CiteSpace, and the results were visualized via network maps.

          Results

          From 2002 to 2022, 480 publications in the database met the criteria. On the country level, China produced the highest number of publications, while the United States had the highest centrality. On the institutional level, University College Cork contributed to the most publications, and John F. Cryan from this university was the key researcher with considerable academic influence. The article, the role of short-chain fatty acids in microbiota-gut-brain, written by Boushra Dalile et al., in 2019 was the most cited article. Furthermore, the journal Nutrients had the maximum number of publications, while Plos One was the most cited journal. “Gut microbiome”, “SCFAs”, and “central nervous system” were the three most frequent keywords. Among them, SCFAs had the highest centrality. “Animal model” was the keyword with the highest burst strength, with the latest burst keywords being “social behavior”, “pathogenesis”, and “insulin sensitive”. In addition, the research topics on SCFAs in CNS diseases from 2002 to 2022 mainly focused on following aspects: SCFAs plays a key role in microbe-gut-brain crosstalk; The classification and definition of SCFAs in the field of CNS; Several CNS diseases that are closely related to SCFAs research; Mechanism and translational studies of SCFAs in the CNS diseases. And the hotspots over the past 5 years have gradually increased the attention to the therapeutic potential of SCFAs in the CNS diseases.

          Conclusion

          The research of SCFAs in CNS diseases is attracting growing attention. However, there is a lack of cooperation between countries and institutions, and additional measures are required to promote cooperation. The current evidence for an association between SCFAs and CNS diseases is preliminary and more work is needed to pinpoint the precise mechanism. Moreover, large-scale clinical trials are needed in the future to define the therapeutic potential of SCFAs in CNS diseases.

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          Most cited references117

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          From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites.

          A compelling set of links between the composition of the gut microbiota, the host diet, and host physiology has emerged. Do these links reflect cause-and-effect relationships, and what might be their mechanistic basis? A growing body of work implicates microbially produced metabolites as crucial executors of diet-based microbial influence on the host. Here, we will review data supporting the diverse functional roles carried out by a major class of bacterial metabolites, the short-chain fatty acids (SCFAs). SCFAs can directly activate G-coupled-receptors, inhibit histone deacetylases, and serve as energy substrates. They thus affect various physiological processes and may contribute to health and disease.
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            The Microbiota-Gut-Brain Axis

            The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson’s disease, and Alzheimer’s disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
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              Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease.

              The intestinal microbiota influence neurodevelopment, modulate behavior, and contribute to neurological disorders. However, a functional link between gut bacteria and neurodegenerative diseases remains unexplored. Synucleinopathies are characterized by aggregation of the protein α-synuclein (αSyn), often resulting in motor dysfunction as exemplified by Parkinson's disease (PD). Using mice that overexpress αSyn, we report herein that gut microbiota are required for motor deficits, microglia activation, and αSyn pathology. Antibiotic treatment ameliorates, while microbial re-colonization promotes, pathophysiology in adult animals, suggesting that postnatal signaling between the gut and the brain modulates disease. Indeed, oral administration of specific microbial metabolites to germ-free mice promotes neuroinflammation and motor symptoms. Remarkably, colonization of αSyn-overexpressing mice with microbiota from PD-affected patients enhances physical impairments compared to microbiota transplants from healthy human donors. These findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for PD.
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                Author and article information

                Contributors
                Journal
                Heliyon
                Heliyon
                Heliyon
                Elsevier
                2405-8440
                19 February 2024
                29 February 2024
                19 February 2024
                : 10
                : 4
                : e26377
                Affiliations
                [a ]Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
                [b ]Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
                [c ]Hunan Provincial Key Laboratory of Neurorestoratology, The Second Affiliated Hospital, Hunan Normal University, Changsha, 410003, Hunan, China
                Author notes
                []Corresponding author. Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China. ztang65@ 123456csu.edu.cn
                [∗∗ ]Corresponding author. Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China. zhipinghu@ 123456csu.edu.cn
                Article
                S2405-8440(24)02408-3 e26377
                10.1016/j.heliyon.2024.e26377
                10906301
                38434086
                f9e04ac3-7121-4991-8d07-e9afba69da2a
                © 2024 The Authors. Published by Elsevier Ltd.

                This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

                History
                : 6 November 2023
                : 11 February 2024
                : 12 February 2024
                Categories
                Research Article

                short-chain fatty acids,central nervous system diseases,bibliometric analysis,hotspots,trends,intellectual structure,visualization

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