{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:10:21Z","timestamp":1793329821504,"version":"4.5.0"},"reference-count":85,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This systematic review investigates the role of the gut microbiota in patients with advanced chronic kidney disease (CKD), specifically stages 4 and 5. Increasing evidence suggests that dysbiosis\u2014an alteration in the normal balance of gut microbial populations\u2014is not merely a secondary consequence of renal decline but a significant driver of disease progression. Such microbial imbalances are closely linked to a range of CKD-associated complications, including systemic inflammation, accumulation of uremic toxins, and heightened cardiovascular risk. Using PRISMA 2020 guidelines, we analyzed 87 peer-reviewed studies published between 2019 and 2025. The review revealed a consistent decline in beneficial microbes such as short-chain fatty acid-producing bacteria were markedly reduced, while populations of uremic toxin-generating microbes were notably increased. This microbial imbalance was associated with elevated concentrations of indoxyl sulfate and p-cresyl sulfate, heightened systemic inflammation, and impaired intestinal barrier integrity. Five conceptual frameworks\u2014including the gut\u2014kidney axis and endotoxemia\u2014inflammation loop\u2014were discussed. Ten microbiome assessment tools were reviewed, including 16S rRNA sequencing and LC-MS\/MS for uremic toxin detection. Although probiotics, prebiotics, and synbiotics are gaining attention as potential therapeutic options, questions remain regarding their long-term efficacy and incorporation into standard clinical practice. Increasing scientific evidence underscores the gut microbiome\u2019s pivotal role in CKD progression and management, reinforcing the need for carefully designed, long-term interventions aimed at restoring a healthier microbial balance to support renal function.<\/jats:p>","DOI":"10.3390\/ijms262110706","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T16:18:42Z","timestamp":1762186722000},"page":"10706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Gut Microbiome in Patients with Chronic Kidney Disease Stages 4 and 5: A Systematic Literature Review"],"prefix":"10.3390","volume":"26","author":[{"given":"Ioana Livia","family":"Suliman","sequence":"first","affiliation":[{"name":"Faculty of Medicine, \u201cOvidius\u201d University of Constanta, 900470 Constanta, Romania"},{"name":"\u201cSfantul Apostol Andrei\u201d Emergency County Clinical Hospital, 900591 Constanta, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florin Gabriel","family":"Panculescu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cOvidius\u201d University of Constanta, 900470 Constanta, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragos","family":"Fasie","sequence":"additional","affiliation":[{"name":"\u201cSfantul Apostol Andrei\u201d Emergency County Clinical Hospital, 900591 Constanta, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan","family":"Cimpineanu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cOvidius\u201d University of Constanta, 900470 Constanta, Romania"},{"name":"\u201cSfantul Apostol Andrei\u201d Emergency County Clinical Hospital, 900591 Constanta, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1420-1034","authenticated-orcid":false,"given":"Andreea","family":"Alexandru","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cOvidius\u201d University of Constanta, 900470 Constanta, Romania"},{"name":"\u201cSfantul Apostol Andrei\u201d Emergency County Clinical Hospital, 900591 Constanta, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelisa","family":"Gafar","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cOvidius\u201d University of Constanta, 900470 Constanta, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stere","family":"Popescu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cOvidius\u201d University of Constanta, 900470 Constanta, Romania"},{"name":"\u201cSfantul Apostol Andrei\u201d Emergency County Clinical Hospital, 900591 Constanta, 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KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","volume":"105","author":"Stevens","year":"2024","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/j.kisu.2021.01.007","article-title":"International Society of Nephrology Global Kidney Health Atlas: Structures, organization, and services for the management of kidney failure in Western Europe","volume":"11","author":"Kelly","year":"2021","journal-title":"Kidney Int."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Popovici, I.A., Orasanu, C.I., Cozaru, G.-C., Ionescu, A.-C., Kajanto, L., Cimpineanu, B., Chisoi, A., Mitroi, A.N., Poinareanu, I., and Voda, R.I. (2025). An Overview of the Etiopathogenic Mechanisms Involved in the Expression of the Oral Microbiota. Clin. Pract., 15.","DOI":"10.3390\/clinpract15040080"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tuta, L., Stanigut, A., Campineanu, B., and Pana, C. (2018). Novel Oral Anticoagulants in Patients with Severe Chronic Kidney Disease, A Real Challenge. Nephrology Dialysis Transplantation, Oxford University Press.","DOI":"10.1093\/ndt\/gfy104.SP305"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Yan, H., Chen, Y., Zhu, H., Huang, W.-H., Cai, X.-H., Li, D., Lv, Y.-J., Zhao, S., Zhou, H.-H., and Luo, F.-Y. (2022). The Relationship among Intestinal Bacteria, Vitamin K and Response of Vitamin K Antagonist: A Review of Evidence and Potential Mechanism. Front. Med., 9.","DOI":"10.3389\/fmed.2022.829304"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/S0140-6736(16)32064-5","article-title":"Chronic Kidney Disease","volume":"389","author":"Webster","year":"2017","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/S0140-6736(13)60687-X","article-title":"Chronic Kidney Disease: Global Dimension and Perspectives","volume":"382","author":"Jha","year":"2013","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0140-6736(20)30045-3","article-title":"Global, Regional, and National Burden of Chronic Kidney Disease, 1990\u20132017: A Systematic Analysis for the Global Burden of Disease Study 2017","volume":"395","author":"Bikbov","year":"2020","journal-title":"Lancet"},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1093\/ndt\/gfv095","article-title":"Altered Intestinal Microbial Flora and Impaired Epithelial Barrier Structure and Function in CKD: The Nature, Mechanisms, Consequences and Potential Treatment","volume":"31","author":"Vaziri","year":"2016","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1681\/ASN.2013080905","article-title":"The Gut Microbiome, Kidney Disease, and Targeted Interventions","volume":"25","author":"Ramezani","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1097\/MNH.0b013e328358c8d5","article-title":"CKD impairs barrier function and alters microbial flora of the intestine: A major link to inflammation and uremic toxicity","volume":"21","author":"Vaziri","year":"2012","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1681\/ASN.2010121220","article-title":"Colonic Contribution to Uremic Solutes","volume":"22","author":"Aronov","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1038\/ki.2009.402","article-title":"Uremic Toxins Originating from Colonic Microbial Metabolism","volume":"76","author":"Evenepoel","year":"2009","journal-title":"Kidney Int. Suppl."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1093\/ndt\/gfq818","article-title":"The Gut\u2013Kidney Axis: Indoxyl Sulfate, P-Cresyl Sulfate and CKD Progression","volume":"26","author":"Meijers","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Barrios, C., Beaumont, M., Pallister, T., Villar, J., Goodrich, J.K., Clark, A., Pascual, J., Ley, R.E., Spector, T.D., and Bell, J.T. (2015). Gut-Microbiota-Metabolite Axis in Early Renal Function Decline. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134311"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gryp, T., Vanholder, R., Vaneechoutte, M., and Glorieux, G. (2017). P-Cresyl Sulfate. Toxins, 9.","DOI":"10.3390\/toxins9020052"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S30","DOI":"10.1053\/j.jrn.2022.12.004","article-title":"Targeting the Gut Microbiota in Kidney Disease: The Future in Renal Nutrition and Metabolism","volume":"33","author":"Lambert","year":"2023","journal-title":"J. Ren. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tan, J., Chen, M., Wang, Y., Tang, Y., and Qin, W. (2022). Emerging trends and focus for the link between the gastrointestinal microbiome and kidney disease. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.946138"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nature12820","article-title":"Diet Rapidly and Reproducibly Alters the Human Gut Microbiome","volume":"505","author":"David","year":"2014","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.phrs.2018.01.013","article-title":"Gut Microbiota, Hypertension and Chronic Kidney Disease: Recent Advances","volume":"144","author":"Sircana","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1068613","DOI":"10.3389\/fphar.2022.1068613","article-title":"Natural products from plants and microorganisms: Novel therapeutics for chronic kidney disease via gut microbiota regulation","volume":"13","author":"Zheng","year":"2023","journal-title":"Front Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12967-018-1756-4","article-title":"Microbiome\u2013Metabolome Reveals the Contribution of Gut\u2013Kidney Axis on Kidney Disease","volume":"17","author":"Chen","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1080\/0886022X.2020.1864404","article-title":"Specific alterations in gut microbiota in patients with chronic kidney disease: An updated systematic review","volume":"43","author":"Zhao","year":"2021","journal-title":"Ren. Fail."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1093\/ndt\/gfp592","article-title":"Free P-Cresyl Sulphate 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_26","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s13668-022-00438-9","article-title":"Dysbiosis in Patients with Chronic Kidney Disease: Let Us Talk About Vitamin K","volume":"11","author":"Kemp","year":"2022","journal-title":"Curr. Nutr. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Jiang, S., Xie, S., Lv, D., Wang, P., He, H., Zhang, T., Zhou, Y., Lin, Q., Zhou, H., and Jiang, J. (2017). Alteration of the Gut Microbiota in Chinese Population with Chronic Kidney Disease. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-02989-2"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/j.1574-6976.2008.00111.x","article-title":"Species Divergence and the Measurement of Microbial Diversity","volume":"32","author":"Lozupone","year":"2008","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrmicro2974","article-title":"The Gut Microbiota\u2014Masters of Host Development and Physiology","volume":"11","author":"Sommer","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/1462-2920.13589","article-title":"Formation of Propionate and Butyrate by the Human Colonic Microbiota","volume":"19","author":"Louis","year":"2017","journal-title":"Environ. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.mib.2013.06.003","article-title":"Faecalibacterium prausnitzii and Human Intestinal Health","volume":"16","author":"Miquel","year":"2013","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nature08821","article-title":"A Human Gut Microbial Gene Catalogue Established by Metagenomic Sequencing","volume":"464","author":"Qin","year":"2010","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.coi.2014.07.003","article-title":"The Cross Talk Between Microbiota and the Immune System: Metabolites Take Center Stage","volume":"30","author":"Shapiro","year":"2014","journal-title":"Curr. Opin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.2337\/db06-1491","article-title":"Metabolic Endotoxemia Initiates Obesity and Insulin Resistance","volume":"56","author":"Cani","year":"2007","journal-title":"Diabetes"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000345969","article-title":"Role of Urea in Intestinal Barrier Dysfunction and Disruption of Epithelial Tight Junction in Chronic Kidney Disease","volume":"37","author":"Vaziri","year":"2013","journal-title":"Am. J. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s11892-017-0841-z","article-title":"Intestinal Microbiota in Type 2 Diabetes and Chronic Kidney Disease","volume":"17","author":"Sabatino","year":"2017","journal-title":"Curr. Diabetes Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1159\/000360010","article-title":"Expansion of Urease- and Uricase-Containing, Indole- and p-Cresol-Forming and Contraction of Short-Chain Fatty Acid-Producing Intestinal Microbiota in ESRD","volume":"39","author":"Wong","year":"2014","journal-title":"Am. J. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Stadlbauer, V., Horvath, A., Ribitsch, W., Schmerb\u00f6ck, B., Schilcher, G., Lemesch, S., Stiegler, P., Rosenkranz, A.R., Fickert, P., and Leber, B. (2017). Structural and Functional Differences in Gut Microbiome Composition in Patients Undergoing Haemodialysis or Peritoneal Dialysis. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-15650-9"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Li, F., Wang, M., Wang, J., Li, R., and Zhang, Y. (2019). Alterations to the Gut Microbiota and Their Correlation with Inflammatory Factors in Chronic Kidney Disease. Front. Cell. Infect. Microbiol., 9.","DOI":"10.3389\/fcimb.2019.00206"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1681\/ASN.2013121283","article-title":"The Cardiovascular Effect of the Uremic Solute Indole-3 Acetic Acid","volume":"26","author":"Dou","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1161\/CIRCRESAHA.116.305360","article-title":"Gut Microbiota-Dependent Trimethylamine N-Oxide (TMAO) Pathway Contributes to Both Development of Renal Insufficiency and Mortality Risk in Chronic Kidney Disease","volume":"116","author":"Tang","year":"2015","journal-title":"Circ. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature09922","article-title":"Gut Flora Metabolism of Phosphatidylcholine Promotes Cardiovascular Disease","volume":"472","author":"Wang","year":"2011","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/nm.3145","article-title":"Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis","volume":"19","author":"Koeth","year":"2013","journal-title":"Nat. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1016\/j.jceh.2014.06.004","article-title":"Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation","volume":"5","author":"Aldridge","year":"2015","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1093\/ndt\/gfr624","article-title":"Disintegration of Epithelial Tight Junction in Uremia: A Likely Cause of CKD-Associated Systemic Inflammation","volume":"27","author":"Vaziri","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1038\/ki.2012.440","article-title":"The Intestinal Microbiota, a Leaky Gut, and Abnormal Immunity in Kidney Disease","volume":"83","author":"Anders","year":"2013","journal-title":"Kidney Int."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/nri2653","article-title":"Intestinal Mucosal Barrier Function in Health and Disease","volume":"9","author":"Turner","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.2337\/db07-1403","article-title":"Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet\u2013Induced Obesity and Diabetes in Mice","volume":"57","author":"Cani","year":"2008","journal-title":"Diabetes"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1093\/ajcn\/86.5.1286","article-title":"A High-Fat Meal Induces Low-Grade Endotoxemia: Evidence of a Novel Mechanism of Postprandial Inflammation","volume":"86","author":"Erridge","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2215\/CJN.04610510","article-title":"Circulating Endotoxemia: A Novel Factor in Systemic Inflammation and Cardiovascular Disease in Chronic Kidney Disease","volume":"6","author":"McIntyre","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1038\/ki.2011.217","article-title":"Renal Microenvironments and Macrophage Phenotypes Determine Progression or Resolution of Renal Inflammation and Fibrosis","volume":"80","author":"Anders","year":"2011","journal-title":"Kidney Int."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1126\/science.1241165","article-title":"The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic Treg Cell Homeostasis","volume":"341","author":"Smith","year":"2013","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1053\/j.ajkd.2005.09.014","article-title":"Serum Albumin, C-Reactive Protein, Interleukin 6, and Fetuin A as Predictors of Malnutrition, Cardiovascular Disease, and Mortality in Patients with ESRD","volume":"47","author":"Honda","year":"2006","journal-title":"Am. J. Kidney Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/j.1525-139X.2010.00784.x","article-title":"Inflammation in End-Stage Renal Disease\u2014What Have We Learned in 10 Years?","volume":"23","author":"Carrero","year":"2010","journal-title":"Semin. Dial."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1038\/nature08530","article-title":"Regulation of Inflammatory Responses by Gut Microbiota and Chemoattractant Receptor GPR43","volume":"461","author":"Maslowski","year":"2009","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Vinolo, M.A.R., Ferguson, G.J., Kulkarni, S., Damoulakis, G., Anderson, K., Bohlooly, Y.M., Stephens, L., Hawkins, P.T., and Curi, R. (2011). SCFAs Induce Neutrophil Chemotaxis through the GPR43 Receptor. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021205"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nature12726","article-title":"Metabolites Produced by Commensal Bacteria Promote Peripheral Regulatory T-Cell Generation","volume":"504","author":"Arpaia","year":"2013","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1053\/j.jrn.2017.02.010","article-title":"The Leaky Gut and Altered Microbiome in Chronic Kidney Disease","volume":"27","author":"Lau","year":"2017","journal-title":"J. Ren. Nutr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.kint.2016.02.025","article-title":"Screening for Muscle Wasting and Dysfunction in Patients with Chronic Kidney Disease","volume":"90","author":"Carrero","year":"2016","journal-title":"Kidney Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"505","DOI":"10.2215\/CJN.03670807","article-title":"Emerging biomarkers for evaluating cardiovascular risk in the chronic kidney disease patient: How do new pieces fit into the uremic puzzle?","volume":"3","author":"Stenvinkel","year":"2008","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"399","DOI":"10.2217\/fmb.13.165","article-title":"Role of Altered Intestinal Microbiota in Systemic Inflammation and Cardiovascular Disease in Chronic Kidney Disease","volume":"9","author":"Mafra","year":"2014","journal-title":"Future Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1136\/gutjnl-2019-319766","article-title":"Aberrant Gut Microbiota Alters Host Metabolome and Impacts Renal Failure in Humans and Rodents","volume":"69","author":"Wang","year":"2020","journal-title":"Gut"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Tsuji, K., Uchida, N., Nakanoh, H., Fukushima, K., Haraguchi, S., Kitamura, S., and Wada, J. (2024). The Gut\u2013Kidney Axis in Chronic Kidney Diseases. Diagnostics, 15.","DOI":"10.20944\/preprints202411.1338.v1"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1053\/j.ajkd.2015.09.027","article-title":"Role of the Gut Microbiome in Uremia: A Potential Therapeutic Target","volume":"67","author":"Ramezani","year":"2016","journal-title":"Am. J. Kidney Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1681\/ASN.2010111210","article-title":"Toll-Like Receptor 4 Promotes Tubular Inflammation in Diabetic Nephropathy","volume":"23","author":"Lin","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.immuni.2011.05.006","article-title":"Toll-Like Receptors and Their Crosstalk with Other Innate Receptors in Infection and Immunity","volume":"34","author":"Kawai","year":"2011","journal-title":"Immunity"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Xu, C., Tsihlis, G., Chau, K., Trinh, K., Rogers, N.M., and Julovi, S.M. (2024). Novel Perspectives in Chronic Kidney Disease-Specific Cardiovascular Disease. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052658"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1161\/CIRCRESAHA.112.278457","article-title":"Cardiorenal Syndrome: The Emerging Role of Protein-Bound Uremic Toxins","volume":"111","author":"Lekawanvijit","year":"2012","journal-title":"Circ. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1681\/ASN.2015030279","article-title":"The Influence of CKD on Colonic Microbial Metabolism","volume":"27","author":"Poesen","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.2215\/CJN.03980609","article-title":"Serum Indoxyl Sulfate Is Associated with Vascular Disease and Mortality in Chronic Kidney Disease Patients","volume":"4","author":"Barreto","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1111\/j.1538-7836.2007.02540.x","article-title":"The Uremic Solute Indoxyl Sulfate Induces Oxidative Stress in Endothelial Cells","volume":"5","author":"Dou","year":"2007","journal-title":"J. Thromb. Haemost."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.lfs.2013.05.008","article-title":"Indoxyl sulfate promotes cardiac fibrosis with enhanced oxidative stress in hypertensive rats","volume":"92","author":"Yisireyili","year":"2013","journal-title":"Life Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1744-9987.2010.00885.x","article-title":"Uremic Toxin Indoxyl Sulfate Inhibits Human Vascular Smooth Muscle Cell Proliferation","volume":"15","author":"Mozar","year":"2011","journal-title":"Ther. Apher. Dial."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1159\/000191468","article-title":"Indoxyl Sulfate Inhibits Nitric Oxide Production and Cell Viability by Inducing Oxidative Stress in Vascular Endothelial Cells","volume":"29","author":"Tumur","year":"2009","journal-title":"Am. J. Nephrol."},{"key":"ref_76","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_77","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1093\/ndt\/gfq580","article-title":"p-Cresyl Sulfate and Indoxyl Sulfate Predict Progression of Chronic Kidney Disease","volume":"26","author":"Wu","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.atherosclerosis.2012.07.012","article-title":"The role of protein-bound uremic toxins on peripheral artery disease and vascular access failure in patients on hemodialysis","volume":"225","author":"Lin","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Lin, C.-J., Wu, V., Wu, P.-C., and Wu, C.-J. (2015). Meta-Analysis of the Associations of p-Cresyl Sulfate (PCS) and Indoxyl Sulfate (IS) with Cardiovascular Events and All-Cause Mortality in Patients with Chronic Renal Failure. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132589"},{"key":"ref_80","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_81","doi-asserted-by":"crossref","unstructured":"Vanholder, R., Pletinck, A., Schepers, E., and Glorieux, G.L. (2018). Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update. Toxins, 10.","DOI":"10.3390\/toxins10010033"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.numecd.2015.03.015","article-title":"Dietary protein-fiber ratio associates with circulating levels of indoxyl sulfate and p-cresyl sulfate in chronic kidney disease patients","volume":"25","author":"Rossi","year":"2015","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.2337\/db08-1637","article-title":"Butyrate Improves Insulin Sensitivity and Increases Energy Expenditure in Mice","volume":"58","author":"Gao","year":"2009","journal-title":"Diabetes"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nrendo.2015.128","article-title":"Short-Chain Fatty Acids in Control of Body Weight and Insulin Sensitivity","volume":"11","author":"Canfora","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/advances\/nmx009","article-title":"Butyrate: A Double-Edged Sword for Health?","volume":"9","author":"Liu","year":"2018","journal-title":"Adv. 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