{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:53:06Z","timestamp":1789753986287,"version":"4.0.1"},"reference-count":177,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T00:00:00Z","timestamp":1618272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union's Horizon 2020 research and innovation programme","award":["860329"],"award-info":[{"award-number":["860329"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/01366, PI20\/00744, PI19\/00815, DTS18\/00032"],"award-info":[{"award-number":["PI18\/01366, PI20\/00744, PI19\/00815, DTS18\/00032"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["RETIC REDinREN RD016\/0009"],"award-info":[{"award-number":["RETIC REDinREN RD016\/0009"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ERA-PerMed-JTC2018","award":["KIDNEY ATTACK AC18\/00064 and PERSTIGAN AC18\/00071"],"award-info":[{"award-number":["KIDNEY ATTACK AC18\/00064 and PERSTIGAN AC18\/00071"]}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["Biomedicina B2017\/BMD-3686 CIFRA2-CM."],"award-info":[{"award-number":["Biomedicina B2017\/BMD-3686 CIFRA2-CM."]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Phosphate is a key uremic toxin associated with adverse outcomes. As chronic kidney disease (CKD) progresses, the kidney capacity to excrete excess dietary phosphate decreases, triggering compensatory endocrine responses that drive CKD-mineral and bone disorder (CKD-MBD). Eventually, hyperphosphatemia develops, and low phosphate diet and phosphate binders are prescribed. Recent data have identified a potential role of the gut microbiota in mineral bone disorders. Thus, parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched in the Th17 cell-inducing taxa segmented filamentous bacteria. Furthermore, the microbiota was required for PTH to stimulate bone formation and increase bone mass, and this was dependent on bacterial production of the short-chain fatty acid butyrate. We review current knowledge on the relationship between phosphate, microbiota and CKD-MBD. Topics include microbial bioactive compounds of special interest in CKD, the impact of dietary phosphate and phosphate binders on the gut microbiota, the modulation of CKD-MBD by the microbiota and the potential therapeutic use of microbiota to treat CKD-MBD through the clinical translation of concepts from other fields of science such as the optimization of phosphorus utilization and the use of phosphate-accumulating organisms.<\/jats:p>","DOI":"10.3390\/nu13041273","type":"journal-article","created":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T10:58:07Z","timestamp":1618311487000},"page":"1273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Phosphate, Microbiota and CKD"],"prefix":"10.3390","volume":"13","author":[{"given":"Chiara","family":"Favero","sequence":"first","affiliation":[{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol","family":"Carriazo","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"},{"name":"Red de Investigacion Renal (REDINREN), Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Cuarental","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"},{"name":"Red de Investigacion Renal (REDINREN), Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Fernandez-Prado","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"},{"name":"Red de Investigacion Renal (REDINREN), Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Gom\u00e1-Garc\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Vanessa","family":"Perez-Gomez","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"},{"name":"Red de Investigacion Renal (REDINREN), Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9805-9523","authenticated-orcid":false,"given":"Alberto","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"},{"name":"Red de Investigacion Renal (REDINREN), Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Fernandez-Fernandez","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"},{"name":"Red de Investigacion Renal (REDINREN), Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7110-6409","authenticated-orcid":false,"given":"Maria Dolores","family":"Sanchez-Ni\u00f1o","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"},{"name":"Red de Investigacion Renal (REDINREN), Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"},{"name":"School of Medicine, Department of Pharmacology and Therapeutics, Universidad Autonoma de Madrid, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1093\/ckj\/sfz007","article-title":"Clarifying the Concept of Chronic Kidney Disease for Non-Nephrologists","volume":"12","author":"Bartsch","year":"2019","journal-title":"Clin. Kidney J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1093\/ckj\/sfaa235","article-title":"The Unaccomplished Mission of Reducing Mortality in Patients on Kidney Replacement Therapy","volume":"13","author":"Ortiz","year":"2020","journal-title":"Clin. Kidney J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1016\/S0140-6736(18)31694-5","article-title":"Forecasting Life Expectancy, Years of Life Lost, and All-Cause and Cause-Specific Mortality for 250 Causes of Death: Reference and Alternative Scenarios for 2016-40 for 195 Countries and Territories","volume":"392","author":"Foreman","year":"2018","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.nefro.2018.09.002","article-title":"The Spanish Society of Nephrology (SENEFRO) Commentary to the Spain GBD 2016 Report: Keeping Chronic Kidney Disease out of Sight of Health Authorities Will Only Magnify the Problem","volume":"39","author":"Ortiz","year":"2019","journal-title":"Nefrologia"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"ERA-EDTA Council (2021). ERACODA Working Group Chronic Kidney Disease is a Key Risk Factor for Severe COVID-19: A Call to Action by the ERA-EDTA. Nephrol. Dial. Transplant., 36, 87\u201394.","DOI":"10.1093\/ndt\/gfaa314"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1093\/ckj\/sfz125","article-title":"Klotho, the Elusive Kidney-Derived Anti-Ageing Factor","volume":"13","author":"Ortiz","year":"2020","journal-title":"Clin. Kidney J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Vanholder, R., Van Laecke, S., Glorieux, G., Verbeke, F., Castillo-Rodriguez, E., and Ortiz, A. (2018). Deleting Death and Dialysis: Conservative Care of Cardio-Vascular Risk and Kidney Function Loss in Chronic Kidney Disease (CKD). Toxins, 10.","DOI":"10.3390\/toxins10060237"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Fernandez-Prado, R., Esteras, R., Perez-Gomez, M.V., Gracia-Iguacel, C., Gonzalez-Parra, E., Sanz, A.B., Ortiz, A., and Sanchez-Ni\u00f1o, M.D. (2017). Nutrients Turned into Toxins: Microbiota Modulation of Nutrient Properties in Chronic Kidney Disease. Nutrients, 9.","DOI":"10.3390\/nu9050489"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.carpath.2012.02.008","article-title":"Phosphate: A Stealthier Killer than Previously Thought?","volume":"21","author":"Egido","year":"2012","journal-title":"Cardiovasc. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Castillo-Rodriguez, E., Fernandez-Prado, R., Esteras, R., Perez-Gomez, M.V., Gracia-Iguacel, C., Fernandez-Fernandez, B., Kanbay, M., Tejedor, A., Lazaro, A., and Ruiz-Ortega, M. (2018). Impact of Altered Intestinal Microbiota on Chronic Kidney Disease Progression. Toxins, 10.","DOI":"10.3390\/toxins10070300"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1093\/ckj\/sfz112","article-title":"Combinations of Mineral and Bone Disorder Markers and Risk of Death and Hospitalizations in the International Dialysis Outcomes and Practice Patterns Study","volume":"13","author":"Fuller","year":"2020","journal-title":"Clin. Kidney J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/ckj\/sfaa089","article-title":"Bone Mineral Density and Mortality in End-Stage Renal Disease Patients","volume":"13","author":"Iseri","year":"2020","journal-title":"Clin. Kidney J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"(2017). Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int. Suppl., 7, 1\u201359.","DOI":"10.1016\/j.kisu.2017.04.001"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/s12325-019-01180-5","article-title":"Albuminuria Downregulation of the Anti-Aging Factor Klotho: The Missing Link Potentially Explaining the Association of Pathological Albuminuria with Premature Death","volume":"37","author":"Ortiz","year":"2020","journal-title":"Adv. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1093\/ndt\/gfx376","article-title":"Albumin Downregulates Klotho in Tubular Cells","volume":"33","author":"Izquierdo","year":"2018","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41581-018-0078-3","article-title":"The Klotho Proteins in Health and Disease","volume":"15","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"519","DOI":"10.2215\/CJN.06080809","article-title":"Understanding Sources of Dietary Phosphorus in the Treatment of Patients with Chronic Kidney Disease","volume":"5","author":"Gutekunst","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1053\/ajkd.1998.v31.pm9531176","article-title":"Association of Serum Phosphorus and Calcium x Phosphate Product with Mortality Risk in Chronic Hemodialysis Patients: A National Study","volume":"31","author":"Block","year":"1998","journal-title":"Am. J. Kidney Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1159\/000468952","article-title":"Fibroblast Growth Factor 23: Mineral Metabolism and Beyond","volume":"190","author":"Grabner","year":"2017","journal-title":"Contrib. Nephrol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"227","DOI":"10.2217\/fmb-2019-0249","article-title":"Unraveling the Drivers and Consequences of Gut Microbiota Disruption in Fabry Disease: The Lyso-Gb3 Link","volume":"15","author":"Politei","year":"2020","journal-title":"Future Microbiol."},{"key":"ref_21","unstructured":"(2021, February 09). 2015\u20132020 Dietary Guidelines for Americans, Available online: https:\/\/health.gov\/sites\/default\/files\/2019-09\/2015-2020_Dietary_Guidelines.pdf."},{"key":"ref_22","unstructured":"Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes (1997). Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride, The National Academies Collection: Reports funded by National Institutes of Health."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1017\/S1368980009004819","article-title":"Habitual High Phosphorus Intakes and Foods with Phosphate Additives Negatively Affect Serum Parathyroid Hormone Concentration: A Cross-Sectional Study on Healthy Premenopausal Women","volume":"12","author":"Kemi","year":"2009","journal-title":"Public Health Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1681\/ASN.2014010104","article-title":"Proteinuria Increases Plasma Phosphate by Altering Its Tubular Handling","volume":"26","author":"Courbebaisse","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.ekir.2019.06.002","article-title":"Strategies for Phosphate Control in Patients with CKD","volume":"4","author":"Barreto","year":"2019","journal-title":"Kidney Int. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1093\/ckj\/sfz082","article-title":"Small Steps towards the Potential of \u201cpreventive\u201d Treatment of Early Phosphate Loading in Chronic Kidney Disease Patients","volume":"12","author":"Bover","year":"2019","journal-title":"Clin. Kidney J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1093\/ckj\/sfz027","article-title":"Short-Term Effects of Sevelamer-Carbonate on Fibroblast Growth Factor 23 and Pulse Wave Velocity in Patients with Normophosphataemic Chronic Kidney Disease Stage 3","volume":"12","author":"Hoekstra","year":"2019","journal-title":"Clin. Kidney J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1007\/s40620-014-0062-3","article-title":"Adherence to Phosphate Binders in Hemodialysis Patients: Prevalence and Determinants","volume":"27","author":"Vrijens","year":"2014","journal-title":"J. Nephrol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1016\/S0140-6736(13)61165-4","article-title":"The Demise of Calcium-Based Phosphate Binders","volume":"382","author":"Ortiz","year":"2013","journal-title":"Lancet"},{"key":"ref_30","first-page":"647","article-title":"Alkalinization Potentiates Vascular Calcium Deposition in an Uremic Milieu","volume":"22","author":"Deudero","year":"2009","journal-title":"J. Nephrol."},{"key":"ref_31","first-page":"573","article-title":"Pharmacological Interactions of Phosphate Binders","volume":"38","author":"Arenas","year":"2018","journal-title":"Nefrologia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1056\/NEJM198607173150304","article-title":"Calcium Carbonate as a Phosphate Binder in Patients with Chronic Renal Failure Undergoing Dialysis","volume":"315","author":"Slatopolsky","year":"1986","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1093\/ckj\/sfz187","article-title":"Evidence in Chronic Kidney Disease\u2013Mineral and Bone Disorder Guidelines: Is It Time to Treat or Time to Wait?","volume":"13","author":"Bover","year":"2020","journal-title":"Clin. Kidney J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1038\/ki.2013.34","article-title":"Effect of a Magnesium-Based Phosphate Binder on Medial Calcification in a Rat Model of Uremia","volume":"83","author":"Behets","year":"2013","journal-title":"Kidney Int."},{"key":"ref_35","first-page":"207","article-title":"Use of Sevelamer in Chronic Kidney Disease: Beyond Phosphorus Control","volume":"35","author":"Zambrano","year":"2015","journal-title":"Nefrologia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1053\/j.jrn.2019.01.004","article-title":"Phosphate Binders and Nonphosphate Effects in the Gastrointestinal Tract","volume":"30","author":"Biruete","year":"2020","journal-title":"J. Ren. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1053\/j.jrn.2009.01.022","article-title":"Sevelamer Hydrochloride Use and Circulating Endotoxin in Hemodialysis Patients: A Pilot Cross-Sectional Study","volume":"19","author":"Sun","year":"2009","journal-title":"J. Ren. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1159\/000135691","article-title":"Endotoxin-Binding Affinity of Sevelamer Hydrochloride","volume":"28","author":"Perianayagam","year":"2008","journal-title":"Am. J. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Dai, L., Meijers, B.K., Bammens, B., de Loor, H., Schurgers, L.J., Qureshi, A.R., Stenvinkel, P., and Evenepoel, P. (2020). Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug-Bug Interaction?. Toxins, 12.","DOI":"10.3390\/toxins12060351"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Fusaro, M., Cozzolino, M., Plebani, M., Iervasi, G., Ketteler, M., Gallieni, M., Aghi, A., Locatelli, F., Cunningham, J., and Salam, S. (2020). Sevelamer Use, Vitamin K Levels, Vascular Calcifications, and Vertebral Fractures in Hemodialysis Patients: Results from the VIKI Study. J. Bone Miner. Res.","DOI":"10.1002\/jbmr.4214"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Bennis, Y., Cluet, Y., Titeca-Beauport, D., El Esper, N., Ure\u00f1a, P., Bodeau, S., Combe, C., Dussol, B., Fouque, D., and Choukroun, G. (2019). The Effect of Sevelamer on Serum Levels of Gut-Derived Uremic Toxins: Results from In Vitro Experiments and A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial. Toxins, 11.","DOI":"10.3390\/toxins11050279"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1093\/ndt\/gfq053","article-title":"Serological Cardiovascular and Mortality Risk Predictors in Dialysis Patients Receiving Sevelamer: A Prospective Study","volume":"25","author":"Brandenburg","year":"2010","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"415","DOI":"10.2169\/internalmedicine.48.1817","article-title":"Sevelamer Decreases Serum Uric Acid Concentration through Adsorption of Uric Acid in Maintenance Hemodialysis Patients","volume":"48","author":"Ohno","year":"2009","journal-title":"Intern. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1161\/CIRCULATIONAHA105.541854","article-title":"Sevelamer Prevents Uremia-Enhanced Atherosclerosis Progression in Apolipoprotein E-Deficient Mice","volume":"112","author":"Phan","year":"2005","journal-title":"Circulation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s10157-017-1504-8","article-title":"Plasma P-Cresol Lowering Effect of Sevelamer in Non-Dialysis CKD Patients: Evidence from a Randomized Controlled Trial","volume":"22","author":"Riccio","year":"2018","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1093\/ndt\/gfr144","article-title":"Lanthanum Carbonate Reduces FGF23 in Chronic Kidney Disease Stage 3 Patients","volume":"26","author":"Navas","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s40265-014-0224-6","article-title":"Next-Generation Phosphate Binders: Focus on Iron-Based Binders","volume":"74","author":"Nastou","year":"2014","journal-title":"Drugs"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"172892","DOI":"10.1016\/j.ejphar.2019.172892","article-title":"Gut Microbiota; an Overlooked Effect of Phosphate Binders","volume":"868","author":"Niknafs","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s12020-018-1605-5","article-title":"Microbiota and Metabolic Diseases","volume":"61","author":"Pascale","year":"2018","journal-title":"Endocrine"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1126\/science.1124234","article-title":"Metagenomic Analysis of the Human Distal Gut Microbiome","volume":"312","author":"Gill","year":"2006","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.phrs.2012.10.007","article-title":"Modulation of Intestinal Barrier by Intestinal Microbiota: Pathological and Therapeutic Implications","volume":"69","author":"Natividad","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1126\/science.aad9378","article-title":"How Colonization by Microbiota in Early Life Shapes the Immune System","volume":"352","author":"Gensollen","year":"2016","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.mam.2017.06.002","article-title":"Interactions between Gut Bacteria and Bile in Health and Disease","volume":"56","author":"Long","year":"2017","journal-title":"Mol. Asp. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1007\/s00018-017-2509-x","article-title":"Mechanisms and Consequences of Intestinal Dysbiosis","volume":"74","author":"Weiss","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nri.2017.7","article-title":"Dysbiosis and the Immune System","volume":"17","author":"Levy","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Jalanka-Tuovinen, J., Salonen, A., Nikkil\u00e4, J., Immonen, O., Kekkonen, R., Lahti, L., Palva, A., and Vos, W.M. (2011). de Intestinal Microbiota in Healthy Adults: Temporal Analysis Reveals Individual and Common Core and Relation to Intestinal Symptoms. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023035"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1038\/nature07336","article-title":"Innate Immunity and Intestinal Microbiota in the Development of Type 1 Diabetes","volume":"455","author":"Wen","year":"2008","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.cell.2016.05.041","article-title":"From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites","volume":"165","author":"Koh","year":"2016","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nrgastro.2012.156","article-title":"The Role of the Gut Microbiota in Nutrition and Health","volume":"9","author":"Flint","year":"2012","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1093\/nutrit\/nux001","article-title":"Dietary Metabolites Derived from Gut Microbiota: Critical Modulators of Epigenetic Changes in Mammals","volume":"75","author":"Bhat","year":"2017","journal-title":"Nutr. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nrd772","article-title":"Histone-Deacetylase Inhibitors: Novel Drugs for the Treatment of Cancer","volume":"1","author":"Johnstone","year":"2002","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"27601","DOI":"10.1074\/jbc.M110.102947","article-title":"Blockade of Dendritic Cell Development by Bacterial Fermentation Products Butyrate and Propionate through a Transporter (Slc5a8)-Dependent Inhibition of Histone Deacetylases","volume":"285","author":"Singh","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1136\/gut.28.10.1221","article-title":"Short Chain Fatty Acids in Human Large Intestine, Portal, Hepatic and Venous Blood","volume":"28","author":"Cummings","year":"1987","journal-title":"Gut"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3611","DOI":"10.1038\/ncomms4611","article-title":"The Short-Chain Fatty Acid Acetate Reduces Appetite via a Central Homeostatic Mechanism","volume":"5","author":"Frost","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"8030","DOI":"10.1073\/pnas.1016088108","article-title":"Short-Chain Fatty Acids and Ketones Directly Regulate Sympathetic Nervous System via G Protein-Coupled Receptor 41 (GPR41)","volume":"108","author":"Kimura","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez Hern\u00e1ndez, M.A., Canfora, E.E., Jocken, J.W.E., and Blaak, E.E. (2019). The Short-Chain Fatty Acid Acetate in Body Weight Control and Insulin Sensitivity. Nutrients, 11.","DOI":"10.3390\/nu11081943"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"393","DOI":"10.3389\/fphar.2020.00393","article-title":"The Contribution of Histone Crotonylation to Tissue Health and Disease: Focus on Kidney Health","volume":"11","author":"Sanz","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1093\/ndt\/gfy009","article-title":"Targeting Epigenetic DNA and Histone Modifications to Treat Kidney Disease","volume":"33","author":"Poveda","year":"2018","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1242\/dmm.024455","article-title":"Histone Lysine Crotonylation during Acute Kidney Injury in Mice","volume":"9","author":"Egido","year":"2016","journal-title":"Dis. Model Mech."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1681\/ASN.2010101073","article-title":"The Inflammatory Cytokines TWEAK and TNF\u03b1 Reduce Renal Klotho Expression through NF\u03baB","volume":"22","author":"Moreno","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"106657","DOI":"10.1016\/j.intimp.2020.106657","article-title":"Sodium Butyrate Protects against Oxidative Stress in Human Nucleus Pulposus Cells via Elevating PPAR\u03b3-Regulated Klotho Expression","volume":"85","author":"Liu","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/ki.2015.332","article-title":"The Inflammatory Cytokine TWEAK Decreases PGC-1\u03b1 Expression and Mitochondrial Function in Acute Kidney Injury","volume":"89","author":"Monsalve","year":"2016","journal-title":"Kidney Int."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/path.5282","article-title":"PGC-1\u03b1 Deficiency Causes Spontaneous Kidney Inflammation and Increases the Severity of Nephrotoxic AKI","volume":"249","author":"Carrasco","year":"2019","journal-title":"J. Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1681\/ASN.2019101029","article-title":"Dietary Fiber Protects against Diabetic Nephropathy through Short-Chain Fatty Acid-Mediated Activation of G Protein-Coupled Receptors GPR43 and GPR109A","volume":"31","author":"Li","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.chom.2018.05.012","article-title":"The Impact of Dietary Fiber on Gut Microbiota in Host Health and Disease","volume":"23","author":"Makki","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nm.3444","article-title":"Gut Microbiota Metabolism of Dietary Fiber Influences Allergic Airway Disease and Hematopoiesis","volume":"20","author":"Trompette","year":"2014","journal-title":"Nat. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1016\/j.bbapap.2008.08.012","article-title":"Acetogenesis and the Wood-Ljungdahl Pathway of CO2 Fixation","volume":"1784","author":"Ragsdale","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1046\/j.1432-1033.2003.03450.x","article-title":"Acryloyl-CoA Reductase from Clostridium Propionicum. An Enzyme Complex of Propionyl-CoA Dehydrogenase and Electron-Transferring Flavoprotein","volume":"270","author":"Hetzel","year":"2003","journal-title":"Eur. J. Biochem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4340","DOI":"10.1128\/JB.00137-06","article-title":"Whole-Genome Transcription Profiling Reveals Genes up-Regulated by Growth on Fucose in the Human Gut Bacterium \u201cRoseburia Inulinivorans\"","volume":"188","author":"Scott","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5186","DOI":"10.1128\/AEM.68.10.5186-5190.2002","article-title":"Acetate Utilization and Butyryl Coenzyme A (CoA):Acetate-CoA Transferase in Butyrate-Producing Bacteria from the Human Large Intestine","volume":"68","author":"Duncan","year":"2002","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.1574-6968.2002.tb11467.x","article-title":"The Microbiology of Butyrate Formation in the Human Colon","volume":"217","author":"Pryde","year":"2002","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Kimura, I., Miyamoto, J., Ohue-Kitano, R., Watanabe, K., Yamada, T., Onuki, M., Aoki, R., Isobe, Y., Kashihara, D., and Inoue, D. (2020). Maternal Gut Microbiota in Pregnancy Influences Offspring Metabolic Phenotype in Mice. Science, 367.","DOI":"10.1126\/science.aaw8429"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.2215\/CJN.02940509","article-title":"P-Cresyl Sulfate and Indoxyl Sulfate in Hemodialysis Patients","volume":"4","author":"Meijers","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Saito, Y., Sato, T., Nomoto, K., and Tsuji, H. (2018). Identification of Phenol- and p-Cresol-Producing Intestinal Bacteria by Using Media Supplemented with Tyrosine and Its Metabolites. FEMS Microbiol. Ecol., 94.","DOI":"10.1093\/femsec\/fiy125"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Pignanelli, M., Just, C., Bogiatzi, C., Dinculescu, V., Gloor, G.B., Allen-Vercoe, E., Reid, G., Urquhart, B.L., Ruetz, K.N., and Velenosi, T.J. (2018). Mediterranean Diet Score: Associations with Metabolic Products of the Intestinal Microbiome, Carotid Plaque Burden, and Renal Function. Nutrients, 10.","DOI":"10.3390\/nu10060779"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1016\/j.kint.2020.01.028","article-title":"Gut Microbiota Generation of Protein-Bound Uremic Toxins and Related Metabolites Is Not Altered at Different Stages of Chronic Kidney Disease","volume":"97","author":"Gryp","year":"2020","journal-title":"Kidney Int."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Glorieux, G., Gryp, T., and Perna, A. (2020). Gut-Derived Metabolites and Their Role in Immune Dysfunction in Chronic Kidney Disease. Toxins, 12.","DOI":"10.3390\/toxins12040245"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1056\/NEJMoa1109400","article-title":"Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk","volume":"368","author":"Tang","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1053\/j.jrn.2015.06.004","article-title":"Trimethylamine N-Oxide From Gut Microbiota in Chronic Kidney Disease Patients: Focus on Diet","volume":"25","author":"Moraes","year":"2015","journal-title":"J. Ren. Nutr."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"14476","DOI":"10.1002\/jcb.28707","article-title":"The Interplay between Microbiota-Dependent Metabolite Trimethylamine N-Oxide, Transforming Growth Factor \u03b2\/SMAD Signaling and Inflammasome Activation in Chronic Kidney Disease Patients: A New Mechanistic Perspective","volume":"120","author":"Atef","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1161\/ATVBAHA.119.313414","article-title":"Trimethylamine-N-Oxide Promotes Vascular Calcification Through Activation of NLRP3 (Nucleotide-Binding Domain, Leucine-Rich-Containing Family, Pyrin Domain-Containing-3) Inflammasome and NF-\u039aB (Nuclear Factor \u039aB) Signals","volume":"40","author":"Zhang","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/ki.2012.476","article-title":"Parathyroid Hormone-Related Protein Protects Renal Tubuloepithelial Cells from Apoptosis by Activating Transcription Factor Runx2","volume":"83","author":"Ardura","year":"2013","journal-title":"Kidney Int."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6659","DOI":"10.1038\/s41598-018-25139-8","article-title":"Contribution of Multidrug and Toxin Extrusion Protein 1 (MATE1) to Renal Secretion of Trimethylamine-N-Oxide (TMAO)","volume":"8","author":"Gessner","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1021\/acs.molpharmaceut.6b00937","article-title":"Identification and Characterization of Trimethylamine-N-Oxide Uptake and Efflux Transporters","volume":"14","author":"Teft","year":"2017","journal-title":"Mol. Pharm."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1161\/ATVBAHA.120.314139","article-title":"Targeted Inhibition of Gut Microbial Trimethylamine N-Oxide Production Reduces Renal Tubulointerstitial Fibrosis and Functional Impairment in a Murine Model of Chronic Kidney Disease","volume":"40","author":"Gupta","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/jcla.20456","article-title":"P-Cresylsulfate and Indoxyl Sulfate Level at Different Stages of Chronic Kidney Disease","volume":"25","author":"Lin","year":"2011","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"111","DOI":"10.5301\/jn.5000111","article-title":"Associations among Chronic Kidney Disease, High Total p-Cresylsulfate and Major Adverse Cardiac Events","volume":"26","author":"Wang","year":"2013","journal-title":"J. Nephrol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1093\/ndt\/gfp592","article-title":"Free P-Cresylsulphate Is a Predictor of Mortality in Patients at Different Stages of Chronic Kidney Disease","volume":"25","author":"Liabeuf","year":"2010","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/bdd.1834","article-title":"Albumin Is the Main Plasma Binding Protein for Indoxyl Sulfate and P-Cresyl Sulfate","volume":"34","author":"Viaene","year":"2013","journal-title":"Biopharm. Drug Dispos."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/tox.22519","article-title":"Bisphenol A Is an Exogenous Toxin That Promotes Mitochondrial Injury and Death in Tubular Cells","volume":"33","author":"Mas","year":"2018","journal-title":"Environ. Toxicol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1159\/000356370","article-title":"Cytotoxic Effects of P-Cresol in Renal Epithelial Tubular Cells","volume":"36","author":"Brocca","year":"2013","journal-title":"Blood Purif."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.toxlet.2015.02.003","article-title":"P-Cresol Mediates Autophagic Cell Death in Renal Proximal Tubular Cells","volume":"234","author":"Lin","year":"2015","journal-title":"Toxicol. Lett."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1093\/ndt\/gfr056","article-title":"Warning: The Unfortunate End of p-Cresol as a Uraemic Toxin","volume":"26","author":"Vanholder","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1093\/ndt\/gfx089","article-title":"P-Cresyl Glucuronide Is a Major Metabolite of p-Cresol in Mouse: In Contrast to p-Cresyl Sulphate, p-Cresyl Glucuronide Fails to Promote Insulin Resistance","volume":"32","author":"Koppe","year":"2017","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1093\/ndt\/gft367","article-title":"P-Cresyl Sulphate Has pro-Inflammatory and Cytotoxic Actions on Human Proximal Tubular Epithelial Cells","volume":"29","author":"Poveda","year":"2014","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.lfs.2012.01.013","article-title":"Indoxyl Sulfate Upregulates Renal Expression of MCP-1 via Production of ROS and Activation of NF-\u039aB, P53, ERK, and JNK in Proximal Tubular Cells","volume":"90","author":"Shimizu","year":"2012","journal-title":"Life Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1093\/ndt\/gfs133","article-title":"P-Cresol Sulfate and Indoxyl Sulfate Induce Similar Cellular Inflammatory Gene Expressions in Cultured Proximal Renal Tubular Cells","volume":"28","author":"Sun","year":"2013","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Sun, C.-Y., Chang, S.-C., and Wu, M.-S. (2012). Uremic Toxins Induce Kidney Fibrosis by Activating Intrarenal Renin-Angiotensin-Aldosterone System Associated Epithelial-to-Mesenchymal Transition. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034026"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3904\/kjim.2016.298","article-title":"Paricalcitol Attenuates Indoxyl Sulfate-Induced Apoptosis through the Inhibition of MAPK, Akt, and NF-KB Activation in HK-2 Cells","volume":"34","author":"Park","year":"2019","journal-title":"Korean J. Intern. Med."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Wang, W.-J., Chang, C.-H., Sun, M.-F., Hsu, S.-F., and Weng, C.-S. (2014). DPP-4 Inhibitor Attenuates Toxic Effects of Indoxyl Sulfate on Kidney Tubular Cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093447"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1111\/nep.12673","article-title":"Upregulation of Nuclear Factor-\u039aB Activity Mediates CYP24 Expression and Reactive Oxygen Species Production in Indoxyl Sulfate-Induced Chronic Kidney Disease","volume":"21","author":"Wang","year":"2016","journal-title":"Nephrology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1177\/0192623318768171","article-title":"Indoxyl Sulfate Induces Apoptosis and Hypertrophy in Human Kidney Proximal Tubular Cells","volume":"46","author":"Ellis","year":"2018","journal-title":"Toxicol. Pathol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1210\/en.2013-1937","article-title":"Indoxyl Sulfate-Induced Activation of (pro)Renin Receptor Is Involved in Expression of TGF-\u03921 and \u03b1-Smooth Muscle Actin in Proximal Tubular Cells","volume":"155","author":"Saito","year":"2014","journal-title":"Endocrinology"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1053\/j.jrn.2014.10.008","article-title":"Indoxyl Sulfate Upregulates Prorenin Expression via Nuclear Factor-\u039aB P65, Signal Transducer and Activator of Transcription 3, and Reactive Oxygen Species in Proximal Tubular Cells","volume":"25","author":"Saito","year":"2015","journal-title":"J. Ren. Nutr."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2050183","DOI":"10.1155\/2019\/2050183","article-title":"Indoxyl Sulfate Induces Renal Fibroblast Activation through a Targetable Heat Shock Protein 90-Dependent Pathway","volume":"2019","author":"Milanesi","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1159\/000346420","article-title":"Indoxyl Sulfate Enhances P53-TGF-\u03921-Smad3 Pathway in Proximal Tubular Cells","volume":"37","author":"Shimizu","year":"2013","journal-title":"Am. J. Nephrol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1681\/ASN.2014010021","article-title":"Protein-Bound Uremic Toxins Induce Tissue Remodeling by Targeting the EGF Receptor","volume":"26","author":"Sun","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Edamatsu, T., Fujieda, A., and Itoh, Y. (2018). Phenyl Sulfate, Indoxyl Sulfate and p-Cresyl Sulfate Decrease Glutathione Level to Render Cells Vulnerable to Oxidative Stress in Renal Tubular Cells. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0193342"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"77722","DOI":"10.18632\/oncotarget.20773","article-title":"Protein-Bound Uremic Toxins Impaired Mitochondrial Dynamics and Functions","volume":"8","author":"Sun","year":"2017","journal-title":"Oncotarget"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1093\/ndt\/gfy111","article-title":"Stabilization of Cell-Cell Junctions by Active Vitamin D Ameliorates Uraemia-Induced Loss of Human Endothelial Barrier Function","volume":"34","author":"Beelen","year":"2019","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Chen, S.-C., Huang, S.-Y., Wu, C.-C., and Hsu, C.-F. (2020). P-Cresylsulfate, the Protein-Bound Uremic Toxin, Increased Endothelial Permeability Partly Mediated by Src-Induced Phosphorylation of VE-Cadherin. Toxins, 12.","DOI":"10.3390\/toxins12020062"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s00418-018-1662-0","article-title":"Protein-Bounded Uremic Toxin p-Cresylsulfate Induces Vascular Permeability Alternations","volume":"149","author":"Tang","year":"2018","journal-title":"Histochem. Cell Biol."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Liu, W.-C., Tomino, Y., and Lu, K.-C. (2018). Impacts of Indoxyl Sulfate and P-Cresol Sulfate on Chronic Kidney Disease and Mitigating Effects of AST-120. Toxins, 10.","DOI":"10.3390\/toxins10090367"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1681\/ASN.2014010042","article-title":"Randomized Placebo-Controlled EPPIC Trials of AST-120 in CKD","volume":"26","author":"Schulman","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1093\/toxsci\/kfu119","article-title":"Hepatic Sulfotransferase as a Nephropreventing Target by Suppression of the Uremic Toxin Indoxyl Sulfate Accumulation in Ischemic Acute Kidney Injury","volume":"141","author":"Saito","year":"2014","journal-title":"Toxicol. Sci."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Chao, C.-T., and Lin, S.-H. (2020). Uremic Vascular Calcification: The Pathogenic Roles and Gastrointestinal Decontamination of Uremic Toxins. Toxins, 12.","DOI":"10.3390\/toxins12120812"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.cca.2018.05.057","article-title":"Effect of Uremic Toxin-Indoxyl Sulfate on the Skeletal System","volume":"484","author":"Liu","year":"2018","journal-title":"Clin. Chim. Acta"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1002\/2211-5463.12258","article-title":"Indoxyl Sulfate, a Uremic Toxin in Chronic Kidney Disease, Suppresses Both Bone Formation and Bone Resorption","volume":"7","author":"Watanabe","year":"2017","journal-title":"FEBS Open Bio"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1042\/CS20160393","article-title":"Protein-Bound Toxins: Has the Cinderella of Uraemic Toxins Turned into a Princess?","volume":"130","author":"Liabeuf","year":"2016","journal-title":"Clin. Sci."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Lau, W.L., Chang, Y., and Vaziri, N.D. (2020). The Consequences of Altered Microbiota in Immune-Related Chronic Kidney Disease. Nephrol. Dial. Transplant.","DOI":"10.1093\/ndt\/gfaa087"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Gryp, T., Huys, G.R.B., Joossens, M., Van Biesen, W., Glorieux, G., and Vaneechoutte, M. (2020). Isolation and Quantification of Uremic Toxin Precursor-Generating Gut Bacteria in Chronic Kidney Disease Patients. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21061986"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1016\/j.clnu.2018.11.029","article-title":"Clinical Association between the Metabolite of Healthy Gut Microbiota, 3-Indolepropionic Acid and Chronic Kidney Disease","volume":"38","author":"Sun","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/nature24661","article-title":"A Gut Bacterial Pathway Metabolizes Aromatic Amino Acids into Nine Circulating Metabolites","volume":"551","author":"Dodd","year":"2017","journal-title":"Nature"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Marzocco, S., Fazeli, G., Di Micco, L., Autore, G., Adesso, S., Dal Piaz, F., Heidland, A., and Di Iorio, B. (2018). Supplementation of Short-Chain Fatty Acid, Sodium Propionate, in Patients on Maintenance Hemodialysis: Beneficial Effects on Inflammatory Parameters and Gut-Derived Uremic Toxins, A Pilot Study (PLAN Study). J. Clin. Med., 7.","DOI":"10.3390\/jcm7100315"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1159\/000495343","article-title":"Effect of Ionic Strength, PH and Chemical Displacers on the Percentage Protein Binding of Protein-Bound Uremic Toxins","volume":"47","author":"Shi","year":"2019","journal-title":"Blood Purif."},{"key":"ref_136","first-page":"1130","article-title":"Lactobacillus Salivarius BP121 Prevents Cisplatin-induced Acute Kidney Injury by Inhibition of Uremic Toxins Such as Indoxyl Sulfate and P-cresol Sulfate via Alleviating Dysbiosis","volume":"45","author":"Lee","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Yang, J., Li, Q., Henning, S.M., Zhong, J., Hsu, M., Lee, R., Long, J., Chan, B., Nagami, G.T., and Heber, D. (2018). Effects of Prebiotic Fiber Xylooligosaccharide in Adenine-Induced Nephropathy in Mice. Mol. Nutr. Food Res., e1800014.","DOI":"10.1002\/mnfr.201800014"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1007\/s11255-019-02291-2","article-title":"The Gut Microbiota and Its Relationship with Chronic Kidney Disease","volume":"51","author":"Plata","year":"2019","journal-title":"Int. Urol. Nephrol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.clnesp.2018.08.010","article-title":"Effect of Lactobacillus Rhamnosus on Serum Uremic Toxins (Phenol and P-Cresol) in Hemodialysis Patients: A Double Blind Randomized Clinical Trial","volume":"28","author":"Eidi","year":"2018","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1093\/ckj\/sfaa157","article-title":"Dietary Potassium and the Kidney: Lifesaving Physiology","volume":"13","author":"Wei","year":"2020","journal-title":"Clin. Kidney J."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1093\/ckj\/sfz129","article-title":"Recurrent Hyperkalaemia Management and Use of Renin-Angiotensin-Aldosterone System Inhibitors: A European Multi-National Targeted Chart Review","volume":"13","author":"Rossignol","year":"2020","journal-title":"Clin. Kidney J."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"320","DOI":"10.3945\/ajcn.113.073148","article-title":"High Dietary Phosphorus Intake Is Associated with All-Cause Mortality: Results from NHANES III123","volume":"99","author":"Chang","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1002\/jsfa.8724","article-title":"Association between the Gut Microbiota and Mineral Metabolism","volume":"98","author":"Skrypnik","year":"2018","journal-title":"J. Sci. Food Agric."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12937-018-0331-4","article-title":"High Phosphorus Intake and Gut-Related Parameters\u2014Results of a Randomized Placebo-Controlled Human Intervention Study","volume":"17","author":"Trautvetter","year":"2018","journal-title":"Nutr. J."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.2217\/nnm-2018-0108","article-title":"Mineralo-Organic Nanoparticles in Health and Disease: An Overview of Recent Findings","volume":"13","author":"Martel","year":"2018","journal-title":"Nanomedicine"},{"key":"ref_146","unstructured":"(2021, February 09). The Facts about Your Favorite Beverages (U.S.)|Phosphorus. Available online: https:\/\/www.pepsicobeveragefacts.com\/home\/phosphorus."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"e01361","DOI":"10.1128\/mBio.01361-14","article-title":"Membership and Behavior of Ultra-Low-Diversity Pathogen Communities Present in the Gut of Humans during Prolonged Critical Illness","volume":"5","author":"Zaborin","year":"2014","journal-title":"mBio"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Ponsuksili, S., Reyer, H., Hadlich, F., Weber, F., Trakooljul, N., Oster, M., Siengdee, P., Mur\u00e1ni, E., Rodehutscord, M., and Camarinha-Silva, A. (2020). Identification of the Key Molecular Drivers of Phosphorus Utilization Based on Host MiRNA-MRNA and Gut Microbiome Interactions. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082818"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1017\/S0954422415000049","article-title":"The Impact of Phosphorus on the Immune System and the Intestinal Microbiota with Special Focus on the Pig","volume":"28","author":"Heyer","year":"2015","journal-title":"Nutr. Res. Rev."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1111\/jpn.13088","article-title":"Phytate Degradation, Intestinal Microbiota, Microbial Metabolites and Immune Values Are Changed in Growing Pigs Fed Diets with Varying Calcium\u2013Phosphorus Concentration and Fermentable Substrates","volume":"103","author":"Heyer","year":"2019","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/j.1574-6941.2010.01017.x","article-title":"Dietary Calcium Phosphate Content and Oat \u03b2-Glucan Influence Gastrointestinal Microbiota, Butyrate-Producing Bacteria and Butyrate Fermentation in Weaned Pigs","volume":"75","author":"Zijlstra","year":"2011","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2527\/jas.2008-1560","article-title":"Ileal Microbiota of Growing Pigs Fed Different Dietary Calcium Phosphate Levels and Phytase Content and Subjected to Ileal Pectin Infusion","volume":"88","author":"Vahjen","year":"2010","journal-title":"J. Anim. Sci."},{"key":"ref_153","first-page":"2792","article-title":"Relationship between Gut Microbiota and Phosphorus Metabolism in Hemodialysis Patients: A Preliminary Exploration","volume":"131","author":"Miao","year":"2018","journal-title":"Chin. Med. J."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/ki.2012.345","article-title":"Chronic Kidney Disease Alters Intestinal Microbial Flora","volume":"83","author":"Vaziri","year":"2013","journal-title":"Kidney Int."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Wu, P.-H., Liu, P.-Y., Chiu, Y.-W., Hung, W.-C., Lin, Y.-T., Lin, T.-Y., Hung, S.-C., Delicano, R.A., Kuo, M.-C., and Wu, C.-Y. (2020). Comparative Gut Microbiome Differences between Ferric Citrate and Calcium Carbonate Phosphate Binders in Patients with End-Stage Kidney Disease. Microorganisms, 8.","DOI":"10.3390\/microorganisms8122040"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"4733","DOI":"10.1074\/jbc.RA119.011913","article-title":"Bile Acid Sequestration Reverses Liver Injury and Prevents Progression of Nonalcoholic Steatohepatitis in Western Diet-Fed Mice","volume":"295","author":"Takahashi","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1111\/dom.13272","article-title":"Glucose-Lowering Effects and Mechanisms of the Bile Acid-Sequestering Resin Sevelamer","volume":"20","author":"Mikkelsen","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1124\/jpet.118.251389","article-title":"The Phosphate Binder Ferric Citrate Alters the Gut Microbiome in Rats with Chronic Kidney Disease","volume":"367","author":"Lau","year":"2018","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.tem.2019.04.005","article-title":"Aligning the Paradoxical Role of Vitamin D in Gastrointestinal Immunity","volume":"30","author":"Cantorna","year":"2019","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"21641","DOI":"10.1038\/s41598-020-77806-4","article-title":"The Potential Role of Vitamin D Supplementation as a Gut Microbiota Modifier in Healthy Individuals","volume":"10","author":"Singh","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1097\/MOG.0b013e32833d4b9f","article-title":"Vitamin D and Mucosal Immune Function","volume":"26","author":"Sun","year":"2010","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.yexmp.2012.04.004","article-title":"Vitamin D Deficiency Decreases the Expression of VDR and Prohibitin in the Lungs of Mice with Allergic Airway Inflammation","volume":"93","author":"Agrawal","year":"2012","journal-title":"Exp. Mol. Pathol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1210\/en.2010-0089","article-title":"Vitamin D Deficiency in Mice Impairs Colonic Antibacterial Activity and Predisposes to Colitis","volume":"151","author":"Lagishetty","year":"2010","journal-title":"Endocrinology"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Chaudhari, S.N., Luo, J.N., Harris, D.A., Aliakbarian, H., Yao, L., Paik, D., Subramaniam, R., Adhikari, A.A., Vernon, A.H., and Kili\u00e7, A. (2020). A Microbial Metabolite Remodels the Gut-Liver Axis Following Bariatric Surgery. Cell Host Microbe.","DOI":"10.1016\/j.chom.2020.12.004"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/s41586-019-1865-0","article-title":"Microbial Bile Acid Metabolites Modulate Gut ROR\u03b3+ Regulatory T Cell Homeostasis","volume":"577","author":"Song","year":"2020","journal-title":"Nature"},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Stacchiotti, V., Rezzi, S., Eggersdorfer, M., and Galli, F. (2020). Metabolic and Functional Interplay between Gut Microbiota and Fat-Soluble Vitamins. Crit. Rev. Food Sci. Nutr., 1\u201322.","DOI":"10.1080\/10408398.2020.1793728"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.kint.2020.03.004","article-title":"Gut Microbiota Orchestrates PTH Action in Bone: Role of Butyrate and T Cells","volume":"98","author":"Massy","year":"2020","journal-title":"Kidney Int."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1172\/JCI133473","article-title":"Parathyroid Hormone\u2013Dependent Bone Formation Requires Butyrate Production by Intestinal Microbiota","volume":"130","author":"Li","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/s41467-019-14148-4","article-title":"PTH Induces Bone Loss via Microbial-Dependent Expansion of Intestinal TNF+ T Cells and Th17 Cells","volume":"11","author":"Yu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_170","first-page":"722","article-title":"Modulation of Intestinal Microbiota, Control of Nitrogen Products and Inflammation by Pre\/Probiotics in Chronic Kidney Disease: A Systematic Review","volume":"35","author":"Lopes","year":"2018","journal-title":"Nutr. Hosp."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Tarayre, C., Nguyen, H.-T., Brognaux, A., Delepierre, A., De Clercq, L., Charlier, R., Michels, E., Meers, E., and Delvigne, F. (2016). Characterisation of Phosphate Accumulating Organisms and Techniques for Polyphosphate Detection: A Review. Sensors, 16.","DOI":"10.3390\/s16060797"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1080\/09593330.2014.934745","article-title":"Identification and Quantification of Microbial Populations in Activated Sludge and Anaerobic Digestion Processes","volume":"36","author":"Reyes","year":"2015","journal-title":"Environ. Technol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1002\/bit.25320","article-title":"Multilevel Correlations in the Biological Phosphorus Removal Process: From Bacterial Enrichment to Conductivity-Based Metabolic Batch Tests and Polyphosphatase Assays","volume":"111","author":"Weissbrodt","year":"2014","journal-title":"Biotechnol. Bioeng."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Quinto, A., Cerqueda-Garc\u00eda, D., Falc\u00f3n, L.I., Gaona, O., Mart\u00ednez-Correa, S., Nieto, J., and G-Santoyo, I. (2020). Gut Microbiome in Children from Indigenous and Urban Communities in M\u00e9xico: Different Subsistence Models, Different Microbiomes. Microorganisms, 8.","DOI":"10.20944\/preprints202007.0668.v1"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.kint.2019.02.012","article-title":"Inhibition of Urinary Stone Disease by a Multi-Species Bacterial Network Ensures Healthy Oxalate Homeostasis","volume":"96","author":"Miller","year":"2019","journal-title":"Kidney Int."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"109729","DOI":"10.1016\/j.envres.2020.109729","article-title":"The Impact of Temperature on the Metabolism of Volatile Fatty Acids by Polyphosphate Accumulating Organisms (PAOs)","volume":"188","author":"Wang","year":"2020","journal-title":"Environ. Res."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"116884","DOI":"10.1016\/j.watres.2021.116884","article-title":"Butyrate Can Support PAOs but Not GAOs in Tropical Climates","volume":"193","author":"Wang","year":"2021","journal-title":"Water Res."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/4\/1273\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:47:24Z","timestamp":1760161644000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/4\/1273"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,13]]},"references-count":177,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["nu13041273"],"URL":"https:\/\/doi.org\/10.3390\/nu13041273","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,13]]}}}