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      Microbiome–metabolome reveals the contribution of gut–kidney axis on kidney disease

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          Abstract

          Dysbiosis represents changes in composition and structure of the gut microbiome community (microbiome), which may dictate the physiological phenotype (health or disease). Recent technological advances and efforts in metagenomic and metabolomic analyses have led to a dramatical growth in our understanding of microbiome, but still, the mechanisms underlying gut microbiome–host interactions in healthy or diseased state remain elusive and their elucidation is in infancy. Disruption of the normal gut microbiota may lead to intestinal dysbiosis, intestinal barrier dysfunction, and bacterial translocation. Excessive uremic toxins are produced as a result of gut microbiota alteration, including indoxyl sulphate, p-cresyl sulphate, and trimethylamine-N-oxide, all implicated in the variant processes of kidney diseases development. This review focuses on the pathogenic association between gut microbiota and kidney diseases (the gut–kidney axis), covering CKD, IgA nephropathy, nephrolithiasis, hypertension, acute kidney injury, hemodialysis and peritoneal dialysis in clinic. Targeted interventions including probiotic, prebiotic and symbiotic measures are discussed for their potential of re-establishing symbiosis, and more effective strategies for the treatment of kidney diseases patients are suggested. The novel insights into the dysbiosis of the gut microbiota in kidney diseases are helpful to develop novel therapeutic strategies for preventing or attenuating kidney diseases and complications.

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          Most cited references74

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          The ribosomal database project (RDP-II): introducing myRDP space and quality controlled public data

          Substantial new features have been implemented at the Ribosomal Database Project in response to the increased importance of high-throughput rRNA sequence analysis in microbial ecology and related disciplines. The most important changes include quality analysis, including chimera detection, for all available rRNA sequences and the introduction of myRDP Space, a new web component designed to help researchers place their own data in context with the RDP's data. In addition, new video tutorials describe how to use RDP features. Details about RDP data and analytical functions can be found at the RDP-II website ().
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            Expansion of Urease- and Uricase-Containing, Indole- and p-Cresol-Forming and Contraction of Short-Chain Fatty Acid-Producing Intestinal Microbiota in ESRD

            Background: Intestinal microbiome constitutes a symbiotic ecosystem that is essential for health, and changes in its composition/function cause various illnesses. Biochemical milieu shapes the structure and function of the microbiome. Recently, we found marked differences in the abundance of numerous bacterial taxa between ESRD and healthy individuals. Influx of urea and uric acid and dietary restriction of fruits and vegetables to prevent hyperkalemia alter ESRD patients' intestinal milieu. We hypothesized that relative abundances of bacteria possessing urease, uricase, and p-cresol- and indole-producing enzymes is increased, while abundance of bacteria containing enzymes converting dietary fiber to short-chain fatty acids (SCFA) is reduced in ESRD. Methods: Reference sets of bacteria containing genes of interest were compiled to family, and sets of intestinal bacterial families showing differential abundances between 12 healthy and 24 ESRD individuals enrolled in our original study were compiled. Overlap between sets was assessed using hypergeometric distribution tests. Results: Among 19 microbial families that were dominant in ESRD patients, 12 possessed urease, 5 possessed uricase, and 4 possessed indole and p-cresol-forming enzymes. Among 4 microbial families that were diminished in ESRD patients, 2 possessed butyrate-forming enzymes. Probabilities of these overlapping distributions were <0.05. Conclusions: ESRD patients exhibited significant expansion of bacterial families possessing urease, uricase, and indole and p-cresol forming enzymes, and contraction of families possessing butyrate-forming enzymes. Given the deleterious effects of indoxyl sulfate, p-cresol sulfate, and urea-derived ammonia, and beneficial actions of SCFA, these changes in intestinal microbial metabolism contribute to uremic toxicity and inflammation.
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              Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism.

              We provide a demonstration in humans of the principle of pharmacometabonomics by showing a clear connection between an individual's metabolic phenotype, in the form of a predose urinary metabolite profile, and the metabolic fate of a standard dose of the widely used analgesic acetaminophen. Predose and postdose urinary metabolite profiles were determined by (1)H NMR spectroscopy. The predose spectra were statistically analyzed in relation to drug metabolite excretion to detect predose biomarkers of drug fate and a human-gut microbiome cometabolite predictor was identified. Thus, we found that individuals having high predose urinary levels of p-cresol sulfate had low postdose urinary ratios of acetaminophen sulfate to acetaminophen glucuronide. We conclude that, in individuals with high bacterially mediated p-cresol generation, competitive O-sulfonation of p-cresol reduces the effective systemic capacity to sulfonate acetaminophen. Given that acetaminophen is such a widely used and seemingly well-understood drug, this finding provides a clear demonstration of the immense potential and power of the pharmacometabonomic approach. However, we expect many other sulfonation reactions to be similarly affected by competition with p-cresol and our finding also has important implications for certain diseases as well as for the variable responses induced by many different drugs and xenobiotics. We propose that assessing the effects of microbiome activity should be an integral part of pharmaceutical development and of personalized health care. Furthermore, we envisage that gut bacterial populations might be deliberately manipulated to improve drug efficacy and to reduce adverse drug reactions.
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                Author and article information

                Contributors
                m18338449312@163.com
                chendanqian2013@163.com
                a612426@foxmail.com
                aliujingru@163.com
                ndvaziri@uci.edu
                yanguo1978@gmail.com
                +86 29 88305273 , zyy@nwu.edu.cn , zhaoyybr@163.com
                Journal
                J Transl Med
                J Transl Med
                Journal of Translational Medicine
                BioMed Central (London )
                1479-5876
                3 January 2019
                3 January 2019
                2019
                : 17
                : 5
                Affiliations
                [1 ]ISNI 0000 0004 1761 5538, GRID grid.412262.1, School of Pharmacy, Faculty of Life Science & Medicine, , Northwest University, ; No. 229 Taibai North Road, Xi’an, 710069 Shaanxi China
                [2 ]ISNI 0000 0001 0668 7243, GRID grid.266093.8, Division of Nephrology and Hypertension, School of Medicine, , University of California Irvine, ; Irvine, CA 92897 USA
                [3 ]ISNI 0000 0001 2188 8502, GRID grid.266832.b, Department of Internal Medicine, , University of New Mexico, ; Albuquerque, 87131 USA
                Author information
                http://orcid.org/0000-0002-0239-7342
                Article
                1756
                10.1186/s12967-018-1756-4
                6317198
                30602367
                44848574-b5a5-4819-95cc-d0ae504e2b66
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 18 September 2018
                : 21 December 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81673578
                Award ID: 81603271
                Award ID: 81872985
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Medicine
                microbiome,gut microbiota,metabolome,kidney diseases,probiotics
                Medicine
                microbiome, gut microbiota, metabolome, kidney diseases, probiotics

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