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      Impact of Gut Dysbiosis on Neurohormonal Pathways in Chronic Kidney Disease

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          Abstract

          Chronic kidney disease (CKD) is a worldwide major health problem. Traditional risk factors for CKD are hypertension, obesity, and diabetes mellitus. Recent studies have identified gut dysbiosis as a novel risk factor for the progression CKD and its complications. Dysbiosis can worsen systemic inflammation, which plays an important role in the progression of CKD and its complications such as cardiovascular diseases. In this review, we discuss the beneficial effects of the normal gut microbiota, and then elaborate on how alterations in the biochemical environment of the gastrointestinal tract in CKD can affect gut microbiota. External factors such as dietary restrictions, medications, and dialysis further promote dysbiosis. We discuss the impact of an altered gut microbiota on neuroendocrine pathways such as the hypothalamus–pituitary–adrenal axis, the production of neurotransmitters and neuroactive compounds, tryptophan metabolism, and the cholinergic anti-inflammatory pathway. Finally, therapeutic strategies including diet modification, intestinal alpha-glucosidase inhibitors, prebiotics, probiotics and synbiotics are reviewed.

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          Most cited references130

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          Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline.

          The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed clinical practice guidelines in 2012 to provide guidance on the evaluation, management, and treatment of chronic kidney disease (CKD) in adults and children who are not receiving renal replacement therapy. The KDIGO CKD Guideline Development Work Group defined the scope of the guideline, gathered evidence, determined topics for systematic review, and graded the quality of evidence that had been summarized by an evidence review team. Searches of the English-language literature were conducted through November 2012. Final modification of the guidelines was informed by the KDIGO Board of Directors and a public review process involving registered stakeholders. The full guideline included 110 recommendations. This synopsis focuses on 10 key recommendations pertinent to definition, classification, monitoring, and management of CKD in adults.
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            Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression.

            The concept that intestinal microbial composition not only affects the health of the gut, but also influences centrally-mediated systems involved in mood, is supported by a growing body of literature. Despite the emergent interest in brain-gut communication and its possible role in the pathogenesis of psychiatric disorders such as depression, particularly subtypes with accompanying gastrointestinal (GI) symptoms, there are few studies dedicated to the search for therapeutic solutions that address both central and peripheral facets of these illnesses. This study aims to assess the potential benefits of the probiotic Bifidobacterium infantis in the rat maternal separation (MS) model, a paradigm that has proven to be of value in the study of stress-related GI and mood disorders. MS adult rat offsprings were chronically treated with bifidobacteria or citalopram and subjected to the forced swim test (FST) to assess motivational state. Cytokine concentrations in stimulated whole blood samples, monoamine levels in the brain, and central and peripheral hypothalamic-pituitary-adrenal (HPA) axis measures were also analysed. MS reduced swim behavior and increased immobility in the FST, decreased noradrenaline (NA) content in the brain, and enhanced peripheral interleukin (IL)-6 release and amygdala corticotrophin-releasing factor mRNA levels. Probiotic treatment resulted in normalization of the immune response, reversal of behavioral deficits, and restoration of basal NA concentrations in the brainstem. These findings point to a more influential role for bifidobacteria in neural function, and suggest that probiotics may have broader therapeutic applications than previously considered. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
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              Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients.

              As a major component of uremic syndrome, cardiovascular disease is largely responsible for the high mortality observed in chronic kidney disease (CKD). Preclinical studies have evidenced an association between serum levels of indoxyl sulfate (IS, a protein-bound uremic toxin) and vascular alterations. The aim of this study is to investigate the association between serum IS, vascular calcification, vascular stiffness, and mortality in a cohort of CKD patients. One-hundred and thirty-nine patients (mean +/- SD age: 67 +/- 12; 60% male) at different stages of CKD (8% at stage 2, 26.5% at stage 3, 26.5% at stage 4, 7% at stage 5, and 32% at stage 5D) were enrolled. Baseline IS levels presented an inverse relationship with renal function and a direct relationship with aortic calcification and pulse wave velocity. During the follow-up period (605 +/- 217 d), 25 patients died, mostly because of cardiovascular events (n = 18). In crude survival analyses, the highest IS tertile was a powerful predictor of overall and cardiovascular mortality (P = 0.001 and 0.012, respectively). The predictive power of IS for death was maintained after adjustment for age, gender, diabetes, albumin, hemoglobin, phosphate, and aortic calcification. The study presented here indicates that IS may have a significant role in the vascular disease and higher mortality observed in CKD patients.
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                Author and article information

                Journal
                Diseases
                Diseases
                diseases
                Diseases
                MDPI
                2079-9721
                13 February 2019
                March 2019
                : 7
                : 1
                : 21
                Affiliations
                [1 ]Division of Nephrology, Department of Medicine, University of California-Irvine, Irvine, CA 92697, USA; n_jazani@ 123456yahoo.com
                [2 ]Department of Internal Medicine, Riverside Community Hospital, University of California-Riverside School of Medicine, Riverside, CA 92501, USA; javadsavoj@ 123456gmail.com
                [3 ]Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA; Michael.Lustgarten@ 123456tufts.edu
                Author notes
                [* ]Correspondence: wllau@ 123456uci.edu (W.L.L.); ndvaziri@ 123456uci.edu (N.D.V.); Tel.: +1-714-456-5142 (W.L.L. & N.D.V.)
                Author information
                https://orcid.org/0000-0002-3118-1073
                Article
                diseases-07-00021
                10.3390/diseases7010021
                6473882
                30781823
                a3e7be68-98bb-475a-8077-7bb7dfeedfe7
                © 2019 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
                : 21 December 2018
                : 08 February 2019
                Categories
                Review

                chronic kidney disease,dysbiosis,gut microbiota,inflammation oxidative stress,prebiotics,probiotics,synbiotics

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