{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:09:56Z","timestamp":1793329796751,"version":"4.5.0"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Chronic kidney disease is associated with increased intestinal barrier permeability, leading to heightened inflammation and oxidative stress. These changes contribute to complications such as cardiovascular disease, anemia, altered mineral metabolism, and CKD progression. Interventions using prebiotics, probiotics, and synbiotics may mitigate dysbiosis and improve intestinal barrier function, Under this premise, the objective of this network meta-analysis was to evaluate the effect of probiotics, prebiotics, and synbiotics in reducing uremic toxins produced by the gut microbiota in CKD patients. Methods: A systematic review and network meta-analysis of randomized clinical trials (RCTs) was performed in the following databases: Web of Science, Scopus, the Cochrane Register of Controlled Trials, and PubMed published between 2019 and 2023. The analysis focused on the use of prebiotics, probiotics, and synbiotics in CKD patients at stages 3 to 5, as per KDIGO guidelines, and their association with reductions in uremic toxins such as Indoxyl Sulfate, p-Cresyl Sulfate, urea, and creatinine. The risk of bias was assessed using the Cochrane risk of bias tool (RoB 2), with evaluations conducted independently by two reviewers, and a third consulted for disagreements. The study follows the PRISMA statement. Results: The studies included 331 patients, primarily male, across CKD stages 3a to 5. The interventions positively impacted the gut microbiota composition, leading to reductions in free and total p-Cresyl Sulfate (SUCRA: 72.6% and 66.2, respectively) and indoxyl sulfate (SUCRA: 88.5% and 83.1%). Conclusions: The findings suggest that modulating the gut microbiota through these interventions can effectively reduce specific uremic toxins. However, further trials are necessary to better understand microbiota modulation and its impact on intestinal bacterial composition (PROSPERO number: CRD42023438901).<\/jats:p>","DOI":"10.3390\/nu17071247","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T04:33:43Z","timestamp":1743654823000},"page":"1247","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Impact of Gut Microbiome Modulation on Uremic Toxin Reduction in Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis"],"prefix":"10.3390","volume":"17","author":[{"given":"Renata","family":"Cedillo-Flores","sequence":"first","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Nefrol\u00f3gicas, Centro M\u00e9dico Nacional Siglo XXI, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3379-0147","authenticated-orcid":false,"given":"Miguel Angel","family":"Cuevas-Budhart","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Nefrol\u00f3gicas, Centro M\u00e9dico Nacional Siglo XXI, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2617-0430","authenticated-orcid":false,"given":"Iv\u00e1n","family":"Cavero-Redondo","sequence":"additional","affiliation":[{"name":"CarVasCare Research Group, Facultad de Enfermer\u00eda de Cuenca, Universidad de Castilla la Mancha, 16002 Cuenca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8101-3898","authenticated-orcid":false,"given":"Maria","family":"Kappes","sequence":"additional","affiliation":[{"name":"Faculty of Healthcare Sciencies, Nursing School, Universidad San Sebasti\u00e1n, Puerto Montt 5501842, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8855-9682","authenticated-orcid":false,"given":"Marcela","family":"\u00c1vila-D\u00edaz","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Nefrol\u00f3gicas, Centro M\u00e9dico Nacional Siglo XXI, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3577-9707","authenticated-orcid":false,"given":"Ram\u00f3n","family":"Paniagua","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Nefrol\u00f3gicas, Centro M\u00e9dico Nacional Siglo XXI, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.kisu.2021.11.003","article-title":"Epidemiology of chronic kidney disease: An update 2022","volume":"12","author":"Kovesdy","year":"2022","journal-title":"Kidney Int. Suppl."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.nefro.2016.05.008","article-title":"Microbiota intestinal en la enfermedad renal cr\u00f3nica","volume":"37","author":"Guldris","year":"2017","journal-title":"Nefrologia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e18991","DOI":"10.1016\/j.heliyon.2023.e18991","article-title":"Chronic kidney disease and gut microbiota","volume":"9","author":"Khiabani","year":"2023","journal-title":"Heliyon"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3390\/diagnostics15010021","article-title":"The Gut\u2013Kidney Axis in Chronic Kidney Diseases","volume":"15","author":"Tsuji","year":"2025","journal-title":"Diagnostics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1093\/ckj\/sfac154","article-title":"Decreasing microbiota-derived uremic toxins to improve CKD outcomes","volume":"15","author":"Beker","year":"2022","journal-title":"Clin. Kidney J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1093\/ndt\/gfl281","article-title":"Intestinal bacterial microflora\u2014A potential source of chronic inflammation in patients with chronic kidney disease","volume":"21","author":"Kotanko","year":"2006","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pivari, F., Mingione, A., Piazzini, G., Ceccarani, C., Ottaviano, E., Brasacchio, C., Cas, M.D., Vischi, M., Cozzolino, M.G., and Fogagnolo, P. (2022). Curcumin Supplementation (Meriva\u00ae) Modulates Inflammation, Lipid Peroxidation and Gut Microbiota Composition in Chronic Kidney Disease. Nutrients, 14.","DOI":"10.3390\/nu14010231"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Filipska, I., Winiarska, A., Knysak, M., and Stomp\u00f3r, T. (2021). Contribution of Gut Microbiota-Derived Uremic Toxins to the Cardiovascular System Mineralization. Toxins, 13.","DOI":"10.3390\/toxins13040274"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Poesen, R., Evenepoel, P., de Loor, H., Delcour, J.A., Courtin, C.M., Kuypers, D., Augustijns, P., Verbeke, K., and Meijers, B. (2016). The influence of prebiotic arabinoxylan oligosaccharides on microbiota derived uremic retention solutes in patients with chronic kidney disease: A randomized controlled trial. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153893"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7577","DOI":"10.1007\/s13197-015-1921-1","article-title":"Probiotics, prebiotics and synbiotics\u2014A review","volume":"52","author":"Pandey","year":"2015","journal-title":"J. Food Sci. Technol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chaudhari, A., and Dwivedi, M.K. (2022). The concept of probiotics, prebiotics, postbiotics, synbiotics, nutribiotics, and pharmabiotics. Probiotics in the Prevention and Management of Human Diseases, Academic Press.","DOI":"10.1016\/B978-0-12-823733-5.00013-1"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1093\/cid\/ciaa662","article-title":"Gut Microbiota Features on Nursing Home Admission Are Associated With Subsequent Acquisition of Antibiotic-resistant Organism Colonization","volume":"71","author":"Wang","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"519","DOI":"10.3233\/JAD-215224","article-title":"Relationship Between the Gut Microbiota and Alzheimer\u2019s Disease: A Systematic Review","volume":"87","year":"2022","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wu, D., Lewis, E.D., Pae, M., and Meydani, S.N. (2019). Nutritional Modulation of Immune Function: Analysis of Evidence, Mechanisms, and Clinical Relevance. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.03160"},{"key":"ref_15","first-page":"145","article-title":"Immunonutrition: Methodology and applications","volume":"31","author":"Zapatera","year":"2015","journal-title":"Nutr. Hosp."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.2215\/CJN.12691117","article-title":"Microbiome and Cardiovascular Disease in CKD","volume":"13","author":"Jovanovich","year":"2018","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.nefro.2018.07.008","article-title":"Contribuci\u00f3n de las toxinas ur\u00e9micas a la fibrosis vascular asociada a la enfermedad renal cr\u00f3nica","volume":"38","author":"Luengo","year":"2018","journal-title":"Nefrolog\u00eda"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1053\/j.jrn.2020.04.008","article-title":"Effects of Probiotics on Malnutrition and Health-Related Quality of Life in Patients Undergoing Peritoneal Dialysis: A Randomized Controlled Trial","volume":"31","author":"Pan","year":"2021","journal-title":"J. Ren. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/ndt\/gfaa335","article-title":"Effect of fructooligosaccharide on endothelial function in CKD patients: A randomized controlled trial","volume":"37","author":"Armani","year":"2022","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"n160","DOI":"10.1136\/bmj.n160","article-title":"PRISMA 2020 explanation and elaboration: Updated guidance and exemplars for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: A revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"156","DOI":"10.2522\/ptj.20070147","article-title":"Scales to Assess the Quality of Randomized Controlled Trials: A Systematic Review","volume":"88","author":"Olivo","year":"2008","journal-title":"Phys. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1002\/sim.6188","article-title":"A design-by-treatment interaction model for network meta-analysis with random inconsistency effects","volume":"33","author":"Jackson","year":"2014","journal-title":"Stat Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/jrsm.1044","article-title":"Consistency and inconsistency in network meta-analysis: Concepts and models for multi-arm studies","volume":"3","author":"Higgins","year":"2012","journal-title":"Res. Synth. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.jclinepi.2010.03.016","article-title":"Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: An overview and tutorial","volume":"64","author":"Salanti","year":"2011","journal-title":"J. Clin. Epidemiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1007\/s00394-018-1785-z","article-title":"An open-label, randomized, placebo-controlled study on the effectiveness of a novel probiotics administration protocol (ProbiotiCKD) in patients with mild renal insufficiency (stage 3a of CKD)","volume":"58","author":"Simeoni","year":"2019","journal-title":"Eur. J. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"De Mauri, A., Carrera, D., Bagnati, M., Rolla, R., Vidali, M., Chiarinotti, D., Pane, M., Amoruso, A., and Del Piano, M. (2022). Probiotics-Supplemented Low-Protein Diet for Microbiota Modulation in Patients with Advanced Chronic Kidney Disease (ProLowCKD): Results from a Placebo-Controlled Randomized Trial. Nutrients, 14.","DOI":"10.3390\/nu14081637"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.phrs.2018.03.003","article-title":"Microbiota metabolites: Pivotal players of cardiovascular damage in chronic kidney disease","volume":"130","author":"Cosola","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1093\/ndt\/gfy171","article-title":"Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: A randomized controlled trial","volume":"34","author":"Ramos","year":"2019","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ebrahim, Z., Proost, S., Tito, R.Y., Raes, J., Glorieux, G., Moosa, M.R., and Blaauw, R. (2022). The Effect of \u00df-Glucan Prebiotic on Kidney Function, Uremic Toxins and Gut Microbiome in Stage 3 to 5 Chronic Kidney Disease (CKD) Predialysis Participants: A Randomized Controlled Trial. Nutrients, 14.","DOI":"10.3390\/nu14040805"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Cosola, C., Rocchetti, M.M., di Bari, I., Acquaviva, P.M., Maranzano, V., Corciulo, S., Di Ciaula, A., Di Palo, D.M., La Forgia, F.M., and Fontana, S. (2021). An Innovative Synbiotic Formulation Decreases Free Serum Indoxyl Sulfate, Small Intestine Permeability and Ameliorates Gastrointestinal Symptoms in a Randomized Pilot Trial in Stage IIIb-IV CKD Patients. Toxins, 13.","DOI":"10.3390\/toxins13050334"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"McFarlane, C., Krishnasamy, R., Stanton, T., Savill, E., Snelson, M., Mihala, G., Kelly, J.T., Morrison, M., Johnson, D.W., and Campbell, K.L. (2021). Synbiotics Easing Renal Failure by Improving Gut Microbiology II (SYNERGY II): A Feasibility Randomized Controlled Trial. Nutrients, 13.","DOI":"10.3390\/nu13124481"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3755","DOI":"10.1007\/s00394-020-02207-2","article-title":"Effect of probiotics on the intestinal microbiota of hemodialysis patients: A randomized trial","volume":"59","author":"Liu","year":"2020","journal-title":"Eur. J. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1053\/j.jrn.2014.05.006","article-title":"Effects of a Symbiotic on Gut Microbiota in Mexican Patients With End-Stage Renal Disease","volume":"24","year":"2014","journal-title":"J. Ren. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lydia, A., Indra, T.A., Rizka, A., and Abdullah, M. (2022). The effects of synbiotics on indoxyl sulphate level, constipation, and quality of life associated with constipation in chronic haemodialysis patients: A randomized controlled trial. BMC Nephrol., 23, Available online: https:\/\/bmcnephrol.biomedcentral.com\/articles\/10.1186\/s12882-022-02890-9.","DOI":"10.1186\/s12882-022-02890-9"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/7\/1247\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:09:05Z","timestamp":1760029745000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/7\/1247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,3]]},"references-count":37,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["nu17071247"],"URL":"https:\/\/doi.org\/10.3390\/nu17071247","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,3]]}}}