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      Chronic Kidney Disease, Gut Dysbiosis, and Constipation: A Burdensome Triplet

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          Abstract

          Gut dysbiosis has been implicated in the progression of chronic kidney disease (CKD). Alterations in the gut environment induced by uremic toxins, the dietary restriction of fiber-rich foods, and multiple drugs may be involved in CKD-related gut dysbiosis. CKD-related gut dysbiosis is considered to be characterized by the expansion of bacterial species producing precursors of harmful uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, and the contraction of species generating beneficial short-chain fatty acids, such as butyrate. Gut-derived uremic toxins cause oxidative stress and pro-inflammatory responses, whereas butyrate exerts anti-inflammatory effects and contributes to gut epithelial integrity. Gut dysbiosis is associated with the disruption of the gut epithelial barrier, which leads to the translocation of endotoxins. Research on CKD-related gut dysbiosis has mainly focused on chronic inflammation and consequent cardiovascular and renal damage. The pathogenic relationship between CKD-related gut dysbiosis and constipation has not yet been investigated in detail. Constipation is highly prevalent in CKD and affects the quality of life of these patients. Under the pathophysiological state of gut dysbiosis, altered bacterial fermentation products may play a prominent role in intestinal dysmotility. In this review, we outline the factors contributing to constipation, such as the gut microbiota and bacterial fermentation; introduce recent findings on the pathogenic link between CKD-related gut dysbiosis and constipation; and discuss potential interventions. This pathogenic link needs to be elucidated in more detail and may contribute to the development of novel treatment options not only for constipation, but also cardiovascular disease in CKD.

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          Most cited references147

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          Linking long-term dietary patterns with gut microbial enterotypes.

          Diet strongly affects human health, partly by modulating gut microbiome composition. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from 98 individuals. Fecal communities clustered into enterotypes distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were strongly associated with long-term diets, particularly protein and animal fat (Bacteroides) versus carbohydrates (Prevotella). A controlled-feeding study of 10 subjects showed that microbiome composition changed detectably within 24 hours of initiating a high-fat/low-fiber or low-fat/high-fiber diet, but that enterotype identity remained stable during the 10-day study. Thus, alternative enterotype states are associated with long-term diet.
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            Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism

            ABSTRACT The formation of SCFA is the result of a complex interplay between diet and the gut microbiota within the gut lumen environment. The discovery of receptors, across a range of cell and tissue types for which short chain fatty acids SCFA appear to be the natural ligands, has led to increased interest in SCFA as signaling molecules between the gut microbiota and the host. SCFA represent the major carbon flux from the diet through the gut microbiota to the host and evidence is emerging for a regulatory role of SCFA in local, intermediary and peripheral metabolism. However, a lack of well-designed and controlled human studies has hampered our understanding of the significance of SCFA in human metabolic health. This review aims to pull together recent findings on the role of SCFA in human metabolism to highlight the multi-faceted role of SCFA on different metabolic systems.
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              What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases

              Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions.
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                Author and article information

                Journal
                Microorganisms
                Microorganisms
                microorganisms
                Microorganisms
                MDPI
                2076-2607
                25 November 2020
                December 2020
                : 8
                : 12
                : 1862
                Affiliations
                [1 ]Sapporo Nephrology Satellite Clinic, 9-2-15, Hassamu 6-jo, Nishi-ku, Sapporo 063-0826, Japan; takuji.snc@ 123456email.plala.or.jp
                [2 ]Sapporo Nephrology Clinic, 20-2-12, Nishimachikita, Nishi-ku, Sapporo 063-0061, Japan; naomi.s@ 123456email.plala.or.jp (N.S.); sawako.snc@ 123456email.plala.or.jp (S.F.)
                Author notes
                [* ]Correspondence: ryota.ikee@ 123456gmail.com
                Author information
                https://orcid.org/0000-0002-3683-5363
                Article
                microorganisms-08-01862
                10.3390/microorganisms8121862
                7760012
                33255763
                7b75593a-2a4d-4d9a-b2f0-7fceee5ea453
                © 2020 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
                : 03 November 2020
                : 24 November 2020
                Categories
                Review

                gut microbiota,dysbiosis,chronic kidney disease,constipation,intestinal motility,gut-derived uremic toxins,inflammation,short-chain fatty acids,butyrate,gut epithelial integrity

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