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      Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

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          Abstract

          The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota–gut–brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer’s disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood–brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.

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          QIIME allows analysis of high-throughput community sequencing data.

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            Gut microbiota in human metabolic health and disease

            Observational findings achieved during the past two decades suggest that the intestinal microbiota may contribute to the metabolic health of the human host and, when aberrant, to the pathogenesis of various common metabolic disorders including obesity, type 2 diabetes, non-alcoholic liver disease, cardio-metabolic diseases and malnutrition. However, to gain a mechanistic understanding of how the gut microbiota affects host metabolism, research is moving from descriptive microbiota census analyses to cause-and-effect studies. Joint analyses of high-throughput human multi-omics data, including metagenomics and metabolomics data, together with measures of host physiology and mechanistic experiments in humans, animals and cells hold potential as initial steps in the identification of potential molecular mechanisms behind reported associations. In this Review, we discuss the current knowledge on how gut microbiota and derived microbial compounds may link to metabolism of the healthy host or to the pathogenesis of common metabolic diseases. We highlight examples of microbiota-targeted interventions aiming to optimize metabolic health, and we provide perspectives for future basic and translational investigations within the nascent and promising research field.
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              Gut microbiota in health and disease.

              Gut microbiota is an assortment of microorganisms inhabiting the length and width of the mammalian gastrointestinal tract. The composition of this microbial community is host specific, evolving throughout an individual's lifetime and susceptible to both exogenous and endogenous modifications. Recent renewed interest in the structure and function of this "organ" has illuminated its central position in health and disease. The microbiota is intimately involved in numerous aspects of normal host physiology, from nutritional status to behavior and stress response. Additionally, they can be a central or a contributing cause of many diseases, affecting both near and far organ systems. The overall balance in the composition of the gut microbial community, as well as the presence or absence of key species capable of effecting specific responses, is important in ensuring homeostasis or lack thereof at the intestinal mucosa and beyond. The mechanisms through which microbiota exerts its beneficial or detrimental influences remain largely undefined, but include elaboration of signaling molecules and recognition of bacterial epitopes by both intestinal epithelial and mucosal immune cells. The advances in modeling and analysis of gut microbiota will further our knowledge of their role in health and disease, allowing customization of existing and future therapeutic and prophylactic modalities.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                21 February 2021
                February 2021
                : 13
                : 2
                : 690
                Affiliations
                [1 ]Department of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kangwon National University, Chuncheon 24341, Korea; umair336@ 123456gmail.com
                [2 ]Department of Food Science, Faculty of Life Sciences, Government College University, Faisalabad 38000, Pakistan; msajidarshad@ 123456gcuf.edu.pk
                [3 ]National Institute of Food Science and Technology, Faculty of Food, Nutrition and Home Sciences, University of Agriculture, Faisalabad 38000, Pakistan; ayshasameen@ 123456uaf.edu.pk
                Author notes
                [* ]Correspondence: deoghwa@ 123456kangwon.ac.kr ; Tel.: +82-33-250-6457
                Author information
                https://orcid.org/0000-0002-5213-2289
                https://orcid.org/0000-0002-3125-675X
                Article
                nutrients-13-00690
                10.3390/nu13020690
                7924846
                33669988
                4ec8c1a4-2f30-4f20-9353-46792b01c76e
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 25 January 2021
                : 17 February 2021
                Categories
                Review

                Nutrition & Dietetics
                gut dysbiosis,microbial metabolites,diet,probiotics,neurodegenerative diseases

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