{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T06:11:52Z","timestamp":1779257512844,"version":"3.51.4"},"reference-count":122,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Chronic kidney disease-associated pruritus (CKD-aP) is a highly prevalent and debilitating symptom in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD), severely impairing quality of life, sleep quality, mental health, and clinical outcomes. Its pathogenesis is multifactorial and remains incompletely understood, involving chronic inflammation, immune imbalance, abnormal neuro-opioid pathways, mineral metabolism disorders and skin barrier damage. The kidney\u2013gut\u2013skin axis has attracted increasing attention as a novel theoretical framework to elucidate the roles of gut microbiota dysbiosis, gut-derived uremic toxins, intestinal barrier impairment and systemic inflammation in the development of CKD-aP. This review summarizes the traditional pathogenic mechanisms of CKD-aP, reviews recent advances linking gut microbial alterations to pruritus-related pathways, and systematically evaluates gut-targeted and metabolism-targeted interventions, including probiotics, prebiotics, synbiotics, AST-120, fecal microbiota transplantation, phytochemicals, Uremia Clearance Granules, and vitamin D-related strategies. Current evidence is mostly associative and is mainly derived from general CKD\/ESKD populations, animal models, and\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies; specific clinical validation in CKD-aP cohorts remains limited. Accordingly, gut microbiome-related mechanisms and interventions remain hypothetical and adjunctive, without established causal relationships or validated standard therapies for CKD-aP. Future studies are required to identify CKD-aP-specific pathological alterations, adopt longitudinal design and multi-omics analysis, conduct mechanistic verification, and perform randomized controlled trials with pruritus as a predefined primary endpoint.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1811786","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:39:18Z","timestamp":1779255558000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut microbiota and the kidney-gut-skin axis in chronic kidney disease-associated pruritus: mechanisms and therapeutic implications"],"prefix":"10.3389","volume":"16","author":[{"given":"Saiping","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyi","family":"Ni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenggui","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riyang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]},{"name":"Key Laboratory of Kidney Disease Prevention and Control Technology","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"B87","doi-asserted-by":"crossref","DOI":"10.3390\/toxins14030197","article-title":"The serum level of IL-31 in patients with chronic kidney disease-associated pruritus: What can we expect","volume":"14","author":"\u015awierczy\u0144ska","year":"2022","journal-title":"Toxins (Basel)"},{"key":"B86","doi-asserted-by":"crossref","DOI":"10.3390\/jcm12062310","article-title":"Serum level of protein-bound uraemic toxins in haemodialysis patients with chronic kidney disease-associated pruritus: Myths and facts","volume":"12","author":"\u015awierczy\u0144ska-Mr\u00f3z","year":"2023","journal-title":"J. Clin. Med."},{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins13080527","article-title":"Chronic kidney disease-associated pruritus","volume":"13","author":"Agarwal","year":"2021","journal-title":"Toxins (Basel)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1093\/ndt\/gfab043","article-title":"Peripheral neuropathy: an important contributor to physical limitation and morbidity in stages 3 and 4 chronic kidney disease","volume":"37","author":"Arnold","year":"2022","journal-title":"Nephrol. Dial Transplant."},{"key":"B3","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/j.jaci.2017.10.045","article-title":"IL-31: a new key player in dermatology and beyond","volume":"141","author":"Ba\u011fci","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/toxins12120741","article-title":"Effects of fecal microbiota transplantation on composition in mice with CKD","volume":"12","author":"Barba","year":"2020","journal-title":"Toxins (Basel)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"12","DOI":"10.23876\/j.krcp.20.185","article-title":"T helper 17 cells in the pathophysiology of acute and chronic kidney disease","volume":"40","author":"Basile","year":"2021","journal-title":"Kidney Res. Clin. Pract."},{"key":"B6","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1146\/annurev-physiol-030212-183811","article-title":"TRPA1: a gatekeeper for inflammation","volume":"75","author":"Bautista","year":"2013","journal-title":"Annu. Rev. Physiol."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2025.2531202","article-title":"A specifically designed multi-biotic reduces uremic toxin generation and improves kidney function","volume":"17","author":"Beau","year":"2025","journal-title":"Gut Microbes"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/nu14122528","article-title":"Faecal microbiota transplantation and chronic kidney disease","volume":"14","author":"Bian","year":"2022","journal-title":"Nutrients"},{"key":"B9","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1111\/j.1600-0625.2009.00844.x","article-title":"Opioids and the skin--where do we stand","volume":"18","author":"Bigliardi","year":"2009","journal-title":"Exp. Dermatol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s11154-011-9194-0","article-title":"Vitamin D and the skin: physiology and pathophysiology","volume":"13","author":"Bikle","year":"2012","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"B18","doi-asserted-by":"crossref","DOI":"10.1002\/jbm4.10405","article-title":"Vitamin D and immune regulation: antibacterial, antiviral, anti-inflammatory","volume":"5","author":"Bishop","year":"2021","journal-title":"JBMR Plus"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02805-22","article-title":"Exploring the relevance between gut microbiota-metabolites profile and chronic kidney disease with distinct pathogenic factor","volume":"11","author":"Chen","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"B12","doi-asserted-by":"publisher","first-page":"26","DOI":"10.5021\/ad.2021.33.1.26","article-title":"Keratinocytes-derived reactive oxygen species play an active role to induce type 2 inflammation of the skin: a pathogenic role of reactive oxygen species at the early phase of atopic dermatitis","volume":"33","author":"Choi","year":"2021","journal-title":"Ann. Dermatol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1681\/asn.0000000000000083","article-title":"Chronic kidney disease is characterized by expansion of a distinct proinflammatory intermediate monocyte subtype and by increased monocyte adhesion to endothelial cells","volume":"34","author":"Cormican","year":"2023","journal-title":"J. Am. Soc Nephrol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/978-3-662-44605-8_16","article-title":"Targeting itch with ligands selective for \u03ba opioid receptors","volume":"226","author":"Cowan","year":"2015","journal-title":"Handb. Exp. Pharmacol."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.01423","article-title":"A purified anthraquinone-glycoside preparation from rhubarb ameliorates type 2 diabetes mellitus by modulating the gut microbiota and reducing inflammation","volume":"10","author":"Cui","year":"2019","journal-title":"Front. Microbiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.22541\/au.160648038.83494811\/v1","article-title":"Interleukin-31: the \"itchy\" cytokine in inflammation and therapy","volume":"76","author":"Datsi","year":"2021","journal-title":"Allergy"},{"key":"B17","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.tins.2010.09.002","article-title":"The multiple pathways for itch and their interactions with pain","volume":"33","author":"Davidson","year":"2010","journal-title":"Trends Neurosci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"3338","DOI":"10.1093\/ndt\/gfr053","article-title":"Interleukin-2 serum levels are elevated in patients with uremic pruritus: a novel finding with practical implications","volume":"26","author":"Fallahzadeh","year":"2011","journal-title":"Nephrol. Dial Transplant."},{"key":"B20","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1007\/s00401-002-0663-0","article-title":"Treatment of experimental autoimmune encephalomyelitis in rat by 1,25-dihydroxyvitamin D3 leads to early effects within the central nervous system","volume":"105","author":"Garcion","year":"2003","journal-title":"Acta Neuropathol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/nrgastro.2017.75","article-title":"Expert consensus document: the International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics","volume":"14","author":"Gibson","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B22","first-page":"14","article-title":"Idiopathic itch, rash, and urticaria\/angioedema merit serum vitamin D evaluation: a descriptive case series","volume":"107","author":"Goetz","year":"2011","journal-title":"W. V Med. J."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1007\/s00403-022-02357-9","article-title":"Reduced serum pyridoxine and 25-hydroxyvitamin D levels in adults with chronic pruritic dermatoses","volume":"315","author":"Gopinath","year":"2023","journal-title":"Arch. Dermatol. Res."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3390\/toxins12090590","article-title":"Gut-derived protein-bound uremic toxins","volume":"12","author":"Graboski","year":"2020","journal-title":"Toxins (Basel)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1007\/s12602-018-9509-5","article-title":"Effects of synbiotics and probiotics supplementation on serum levels of endotoxin, heat shock protein 70 antibodies and inflammatory markers in hemodialysis patients: a randomized double-blinded controlled trial","volume":"12","author":"Haghighat","year":"2020","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"B26","doi-asserted-by":"publisher","first-page":"F1211","DOI":"10.1152\/ajprenal.00298.2018","article-title":"Chronic kidney disease and the gut microbiome","volume":"316","author":"Hobby","year":"2019","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"964","DOI":"10.3892\/etm.2019.7588","article-title":"Clinical features and risk factors of pruritus in patients with chronic renal failure","volume":"18","author":"Hu","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"7353","DOI":"10.1021\/acs.jafc.1c01547","article-title":"Preventive effects of lactobacillus mixture against chronic kidney disease progression through enhancement of beneficial bacteria and downregulation of gut-derived uremic toxins","volume":"69","author":"Huang","year":"2021","journal-title":"J. Agric. Food. Chem."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.01092","article-title":"Rhubarb enema improved colon mucosal barrier injury in 5\/6 nephrectomy rats may associate with gut microbiota modification","volume":"11","author":"Ji","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2025.2495859","article-title":"Gut microbes-spinal connection is required for itch sensation","volume":"17","author":"Jin","year":"2025","journal-title":"Gut Microbes"},{"key":"B31","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1111\/1346-8138.12895","article-title":"Effect of topical vitamin D on chronic kidney disease-associated pruritus: an open-label pilot study","volume":"42","author":"Jung","year":"2015","journal-title":"J. Dermatol."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.638325","article-title":"Interleukin-31 as a clinical target for pruritus treatment","volume":"8","author":"Kabashima","year":"2021","journal-title":"Front. Med. (Lausanne)"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12051107","article-title":"Non-melanoma skin cancer and vitamin D: the \"lost sunlight\" paradox and the oxidative stress explanation","volume":"12","author":"Karampinis","year":"2023","journal-title":"Antioxidants (Basel)"},{"key":"B34","doi-asserted-by":"publisher","first-page":"177","DOI":"10.23876\/j.krcp.22.153","article-title":"Vitamin D and narrowband ultraviolet B phototherapy for chronic kidney disease-associated pruritus","volume":"43","author":"Kee","year":"2024","journal-title":"Kidney Res. Clin. Pract."},{"key":"B35","article-title":"Frontiers in neuroscience role of PAR-2 in neuroimmune communication and itch","volume-title":"Itch: Mechanisms and Treatment","author":"Kempkes","year":"2014"},{"key":"B36","doi-asserted-by":"publisher","first-page":"12036","DOI":"10.1096\/fj.201900016rr","article-title":"IL-6\/p-BTK\/p-ERK signaling mediates calcium phosphate-induced pruritus","volume":"33","author":"Keshari","year":"2019","journal-title":"FASEB J."},{"key":"B37","doi-asserted-by":"publisher","first-page":"i1","DOI":"10.1093\/ckj\/sfab142","article-title":"Epidemiology and burden of chronic kidney disease-associated pruritus","volume":"14","author":"Kim","year":"2021","journal-title":"Clin. Kidney J."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24021559","article-title":"Pathogenesis and treatment of pruritus associated with chronic kidney disease and cholestasis","volume":"24","author":"Kim","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"10844","DOI":"10.1096\/fj.201900730r","article-title":"Indoxyl sulfate-induced TNF-\u03b1 is regulated by crosstalk between the aryl hydrocarbon receptor, NF-\u03baB, and SOCS2 in human macrophages","volume":"33","author":"Kim","year":"2019","journal-title":"FASEB J."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3057","DOI":"10.1038\/s41598-017-03130-z","article-title":"Indoxyl sulfate (IS)-mediated immune dysfunction provokes endothelial damage in patients with end-stage renal disease (ESRD)","volume":"7","author":"Kim","year":"2017","journal-title":"Sci. Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1093\/ndt\/gfx161.mp031","article-title":"Uremic solutes of indoxyl sulfate and p-cresol enhance protease-activated receptor-2 expression in vitro and in vivo in keratinocytes","volume":"40","author":"Kim","year":"2021","journal-title":"Hum. Exp. Toxicol."},{"key":"B42","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1111\/hdi.12158","article-title":"Pruritus in hemodialysis patients: results from the Japanese Dialysis Outcomes and Practice Patterns Study (JDOPPS)","volume":"18","author":"Kimata","year":"2014","journal-title":"Hemodial. Int."},{"key":"B43","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1093\/ndt\/gfi204","article-title":"The role of micro-inflammation in the pathogenesis of uraemic pruritus in haemodialysis patients","volume":"21","author":"Kimmel","year":"2006","journal-title":"Nephrol. Dial Transplant."},{"key":"B44","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/j.jid.2025.06.640","article-title":"Gut microbial signatures associated with uremic pruritus in hemodialysis patients","volume":"58","author":"Ko","year":"2025","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/j.jaad.2014.08.004","article-title":"Interleukin-31 is associated with uremic pruritus in patients receiving hemodialysis","volume":"71","author":"Ko","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1136\/gutjnl-2024-334634","article-title":"Toxic microbiome and progression of chronic kidney disease: insights from a longitudinal CKD-microbiome study","volume":"74","author":"Laiola","year":"2025","journal-title":"Gut"},{"key":"B47","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1159\/000381990","article-title":"The gut as a source of inflammation in chronic kidney disease","volume":"130","author":"Lau","year":"2015","journal-title":"Nephron"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1080\/0886022x.2025.2506810","article-title":"Impact of gut microbiota in chronic kidney disease: natural polyphenols as beneficial regulators","volume":"47","author":"Li","year":"2025","journal-title":"Ren Fail."},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25189983","article-title":"Evaluating the role of vitamin D in alleviating chronic pruritus: a meta-analysis","volume":"25","author":"Li","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.phymed.2018.12.018","article-title":"Improved dialysis removal of protein-bound uremic toxins by salvianolic acids","volume":"57","author":"Li","year":"2019","journal-title":"Phytomedicine"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3390\/toxins13100702","article-title":"Effects of uremic clearance granules in uremic pruritus: A meta-analysis","volume":"13","author":"Lu","year":"2021","journal-title":"Toxins (Basel)"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3390\/toxins15080499","article-title":"Gut microbiota interventions to retain residual kidney function","volume":"15","author":"Mafra","year":"2023","journal-title":"Toxins (Basel)"},{"key":"B53","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1002\/glia.10168","article-title":"Cytokine-stimulated inducible nitric oxide synthase expression in astroglia: Role of Erk mitogen-activated protein kinase and NF-kappaB","volume":"41","author":"Marcus","year":"2003","journal-title":"Glia"},{"key":"B54","doi-asserted-by":"publisher","first-page":"152","DOI":"10.12938\/bmfh.2022-078","article-title":"Dietary phytochemicals, gut microbiota composition, and health outcomes in human and animal models","volume":"42","author":"Mirmohammadali","year":"2023","journal-title":"Biosci. Microbiota Food. Health"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3390\/nu13113721","article-title":"Plant-based versus animal-based low protein diets in the management of chronic kidney disease","volume":"13","author":"Mocanu","year":"2021","journal-title":"Nutrients"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3390\/medicines6040110","article-title":"Role of dysregulated ion channels in sensory neurons in chronic kidney disease-associated pruritus","volume":"6","author":"Momose","year":"2019","journal-title":"Medicines (Basel)"},{"key":"B57","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.1093\/oxfordjournals.ndt.a027092","article-title":"Pruritus and skin hydration during dialysis","volume":"11","author":"Morton","year":"1996","journal-title":"Nephrol. Dial Transplant."},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2021.101484","article-title":"Intestinal microbiota and diabetic kidney diseases: The role of microbiota and derived metabolites inmodulation of renal inflammation and disease progression","volume":"35","author":"Mosterd","year":"2021","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"B59","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1093\/nutrit\/nux077","article-title":"Vitamin D supplementation for improvement of chronic low-grade inflammation in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials","volume":"76","author":"Mousa","year":"2018","journal-title":"Nutr. Rev."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1161\/01.res.0000171451.88616.c2","article-title":"Proinflammatory activation of macrophages by basic calcium phosphate crystals via protein kinase C and MAP kinase pathways: A vicious cycle of inflammation and arterial calcification","volume":"96","author":"Nadra","year":"2005","journal-title":"Circ. Res."},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26031335","article-title":"Health-improving effects of polyphenols on the human intestinal microbiota: A review","volume":"26","author":"Nemzer","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"B62","doi-asserted-by":"publisher","first-page":"179","DOI":"10.4168\/aair.2013.5.4.179","article-title":"The clinical impact of vitamin d in children with atopic dermatitis","volume":"5","author":"Oh","year":"2013","journal-title":"Allergy Asthma Immunol. Res."},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2020.155369","article-title":"Elevated interleukin 31 serum levels in hemodialysis patients are associated with uremic pruritus","volume":"138","author":"Oweis","year":"2021","journal-title":"Cytokine"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1092729","article-title":"Effects of several flavonoids on human gut microbiota and its metabolism by in vitro simulated fermentation","volume":"14","author":"Pan","year":"2023","journal-title":"Front. Microbiol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"2207","DOI":"10.1096\/fj.14-268342","article-title":"Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: Relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior","volume":"29","author":"Patrick","year":"2015","journal-title":"FASEB J."},{"key":"B66","doi-asserted-by":"publisher","first-page":"E228","DOI":"10.1152\/ajpendo.1984.247.2.e228","article-title":"Alterations in rat epidermis provoked by chronic vitamin D deficiency","volume":"247","author":"Pavlovitch","year":"1984","journal-title":"Am. J. Physiol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"24400","DOI":"10.1021\/acs.jafc.4c04456","article-title":"Butyrate inhibits the HDAC8\/NF-\u03baB pathway to enhance Slc26a3 expression and improve the intestinal epithelial barrier to relieve colitis","volume":"72","author":"Peng","year":"2024","journal-title":"J. Agric. Food. Chem."},{"key":"B68","doi-asserted-by":"publisher","first-page":"39","DOI":"10.2174\/1871530323666230511140514","article-title":"Gut-skin axis: Unravelling the link between gut microbiome and chronic kidney disease-related skin lesions","volume":"24","author":"Qiao","year":"2024","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10727","article-title":"Advanced glycation end products and bone metabolism in patients with chronic kidney disease","volume":"7","author":"Quadros","year":"2023","journal-title":"JBMR Plus"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3390\/toxins14030183","article-title":"The role of dietary fiber and gut microbiome modulation in progression of chronic kidney disease","volume":"14","author":"Ranganathan","year":"2022","journal-title":"Toxins (Basel)"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202001936","article-title":"Alterations of the human gut microbiome in chronic kidney disease","volume":"7","author":"Ren","year":"2020","journal-title":"Adv. Sci. (Weinh)"},{"key":"B72","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1186\/1471-2369-15-106","article-title":"Synbiotics easing renal failure by improving gut microbiology (SYNERGY): A randomized trial","volume":"11","author":"Rossi","year":"2016","journal-title":"Clin. J. Am. Soc Nephrol."},{"key":"B73","doi-asserted-by":"publisher","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":"B74","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1186\/s12882-020-01928-0","article-title":"Vascular calcification in skin and subcutaneous tissue in patients with chronic and end-stage kidney disease","volume":"21","author":"Ruderman","year":"2020","journal-title":"BMC Nephrol."},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3390\/toxins13040252","article-title":"The impact of CKD on uremic toxins and gut microbiota","volume":"13","author":"Rysz","year":"2021","journal-title":"Toxins (Basel)"},{"key":"B76","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1093\/ndt\/gfu287","article-title":"Alterations of intestinal barrier and microbiota in chronic kidney disease","volume":"30","author":"Sabatino","year":"2015","journal-title":"Nephrol. Dial Transplant."},{"key":"B77","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1053\/j.ajkd.2016.07.031","article-title":"Sleep disorders, restless legs syndrome, and uremic pruritus: Diagnosis and treatment of common symptoms in dialysis patients","volume":"69","author":"Scherer","year":"2017","journal-title":"Am. J. Kidney Dis."},{"key":"B78","doi-asserted-by":"publisher","first-page":"i23","DOI":"10.1093\/ckj\/sfab200","article-title":"Unravelling the pathophysiology of chronic kidney disease-associated pruritus","volume":"14","author":"Schricker","year":"2021","journal-title":"Clin. Kidney J."},{"key":"B79","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1021\/bi901786x","article-title":"The uremic toxin 3-indoxyl sulfate is a potent endogenous agonist for the human aryl hydrocarbon receptor","volume":"49","author":"Schroeder","year":"2010","journal-title":"Biochemistry"},{"key":"B80","doi-asserted-by":"publisher","first-page":"10188","DOI":"10.1073\/pnas.90.21.10188","article-title":"Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming","volume":"90","author":"Seder","year":"1993","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B81","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1053\/j.jrn.2012.12.007","article-title":"The effect of ergocalciferol on uremic pruritus severity: A randomized controlled trial","volume":"23","author":"Shirazian","year":"2013","journal-title":"J. Ren Nutr."},{"key":"B82","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1007\/978-3-662-46875-3_4807","article-title":"Proteinase-activated receptor-2 in human skin: Tissue distribution and activation of keratinocytes by mast cell tryptase","volume":"8","author":"Steinhoff","year":"1999","journal-title":"Exp. Dermatol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1681\/asn.2014111063","article-title":"Serum trimethylamine-N-oxide is elevated in CKD and correlates with coronary atherosclerosis burden","volume":"27","author":"Stubbs","year":"2016","journal-title":"J. Am. Soc Nephrol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.xkme.2020.08.011","article-title":"Self-reported pruritus and clinical, dialysis-related, and patient-reported outcomes in hemodialysis patients","volume":"3","author":"Sukul","year":"2021","journal-title":"Kidney Med."},{"key":"B85","doi-asserted-by":"publisher","first-page":"673","DOI":"10.2215\/cjn.09600818","article-title":"Pruritus and patient reported outcomes in non-dialysis CKD","volume":"14","author":"Sukul","year":"2019","journal-title":"Clin. J. Am. Soc Nephrol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1146\/annurev.immunol.21.120601.140942","article-title":"Molecular mechanisms regulating Th1 immune responses","volume":"21","author":"Szabo","year":"2003","journal-title":"Annu. Rev. Immunol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"13728","DOI":"10.1523\/jneurosci.3637-11.2011","article-title":"Vitamin D deficiency promotes skeletal muscle hypersensitivity and sensory hyperinnervation","volume":"31","author":"Tague","year":"2011","journal-title":"J. Neurosci."},{"key":"B90","doi-asserted-by":"publisher","first-page":"113433","DOI":"10.26226\/m.641999e15cbd02001a87da48","article-title":"Sensory neuronal STAT3 is critical for IL-31 receptor expression and inflammatory itch","volume":"42","author":"Takahashi","year":"2023","journal-title":"Cell Rep."},{"key":"B91","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1186\/s12967-023-04455-2","article-title":"The gut microbiome tango in the progression of chronic kidney disease and potential therapeutic strategies","volume":"21","author":"Tang","year":"2023","journal-title":"J. Transl. Med."},{"key":"B92","doi-asserted-by":"publisher","first-page":"181","DOI":"10.7762\/cnr.2021.10.3.181","article-title":"Vitamin D and the gut microbiota: A narrative literature review","volume":"10","author":"Tangestani","year":"2021","journal-title":"Clin. Nutr. Res."},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.3390\/life11050419","article-title":"Chronic kidney disease as a systemic inflammatory syndrome: Update on mechanisms involved and potential treatment","volume":"11","author":"Tinti","year":"2021","journal-title":"Life. (Basel)"},{"key":"B94","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1038\/s41590-025-02227-2","article-title":"The role of gut microbial metabolites in the T cell lifecycle","volume":"26","author":"Tran","year":"2025","journal-title":"Nat. Immunol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1146\/annurev.iy.13.040195.001343","article-title":"Interleukin-12: A proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity","volume":"13","author":"Trinchieri","year":"1995","journal-title":"Annu. Rev. Immunol."},{"key":"B96","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1038\/s41385-022-00524-9","article-title":"Gut-derived short-chain fatty acids modulate skin barrier integrity by promoting keratinocyte metabolism and differentiation","volume":"15","author":"Trompette","year":"2022","journal-title":"Mucosal Immunol."},{"key":"B97","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/bs.mie.2023.01.001","article-title":"Molecular regulation of PLC\u03b2 signaling","volume":"682","author":"Ubeysinghe","year":"2023","journal-title":"Methods Enzymol."},{"key":"B98","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12979-025-00514-y","article-title":"Gut-vitamin D interplay: Key to mitigating immunosenescence and promoting healthy ageing","volume":"22","author":"Ullah","year":"2025","journal-title":"Immun. Ageing"},{"key":"B99","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1097\/mnh.0000000000000824","article-title":"Pruritus in chronic kidney disease","volume":"31","author":"Uppal","year":"2022","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"B100","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1159\/000343886","article-title":"Uremic plasma impairs barrier function and depletes the tight junction protein constituents of intestinal epithelium","volume":"36","author":"Vaziri","year":"2012","journal-title":"Am. J. Nephrol."},{"key":"B101","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1016\/j.ekir.2020.04.027","article-title":"Ckd-associated pruritus: New insights into diagnosis, pathogenesis, and management","volume":"5","author":"Verduzco","year":"2020","journal-title":"Kidney Int. Rep."},{"key":"B102","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1002\/jcsm.12129","article-title":"Toll-like receptor 4 signalling mediates inflammation in skeletal muscle of patients with chronic kidney disease","volume":"8","author":"Verzola","year":"2017","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12072474","article-title":"Endogenous opioid imbalance as a potential factor involved in the pathogenesis of chronic kidney disease-associated pruritus in dialysis patients","volume":"12","author":"Wala-Zieli\u0144ska","year":"2023","journal-title":"J. Clin. Med."},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2025.08.036","article-title":"Enhanced sleep quality and reduced indoxyl sulfate levels following probiotic supplementation were linked to gut microbiota modulation in hemodialysis patients","author":"Wang","year":"2025","journal-title":"J. Formos Med. Assoc"},{"key":"B104","doi-asserted-by":"publisher","first-page":"423","DOI":"10.3920\/bm2014.0088","article-title":"The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: A randomised, double-blind, placebo-controlled trial","volume":"6","author":"Wang","year":"2015","journal-title":"Benef Microbes"},{"key":"B105","doi-asserted-by":"publisher","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":"B107","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.92","article-title":"p-Cresyl sulfate, a uremic toxin, causes vascular endothelial and smooth muscle cell damages by inducing oxidative stress","volume":"3","author":"Watanabe","year":"2015","journal-title":"Pharmacol. Res. Perspect."},{"key":"B108","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/ki.2012.448","article-title":"p-Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase","volume":"83","author":"Watanabe","year":"2013","journal-title":"Kidney Int."},{"key":"B109","doi-asserted-by":"crossref","first-page":"263","DOI":"10.2147\/IJNRD.S191156","article-title":"Chronic kidney disease-mineral and bone disorder (CKD-MBD): Current perspectives","volume":"12","author":"Waziri","year":"2019","journal-title":"Int. J. Nephrol. Renovasc Dis."},{"key":"B110","doi-asserted-by":"publisher","first-page":"2368","DOI":"10.1111\/jdv.16360","article-title":"Opioid receptors expression in the skin of haemodialysis patients suffering from uraemic pruritus","volume":"34","author":"Wieczorek","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol"},{"key":"B111","doi-asserted-by":"publisher","first-page":"4236","DOI":"10.18632\/aging.205580","article-title":"AST-120 improved uremic pruritus by lowering indoxyl sulfate and inflammatory cytokines in hemodialysis patients","volume":"16","author":"Wu","year":"2024","journal-title":"Aging (Albany NY)"},{"key":"B112","doi-asserted-by":"publisher","first-page":"102","DOI":"10.3748\/wjg.v21.i1.102","article-title":"Fecal microbiota transplantation broadening its application beyond intestinal disorders","volume":"21","author":"Xu","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"B113","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1159\/000453673","article-title":"Effect of AST-120 in chronic kidney disease treatment: Still a controversy","volume":"135","author":"Yamaguchi","year":"2017","journal-title":"Nephron"},{"key":"B114","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1007\/s004030000124","article-title":"Ultraviolet B radiation downregulates inducible nitric oxide synthase expression induced by interferon-gamma or tumor necrosis factor-alpha in murine keratinocyte Pam 212 cells","volume":"292","author":"Yamaoka","year":"2000","journal-title":"Arch. Dermatol. Res."},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.820664","article-title":"Red nucleus interleukin-6 evokes tactile allodynia in male rats through modulating spinal pro-inflammatory and anti-inflammatory cytokines","volume":"15","author":"Yang","year":"2022","journal-title":"Front. Mol. Neurosci."},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116431","article-title":"Time-dependent laxative effect of sennoside A, the core functional component of rhubarb, is attributed to gut microbiota and aquaporins","volume":"311","author":"Zhang","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"B119","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1016\/j.chom.2025.08.014","article-title":"Gut-microbiota-derived indole sulfate promotes heart failure in chronic kidney disease","volume":"33","author":"Zhang","year":"2025","journal-title":"Cell Host Microbe"},{"key":"B118","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1080\/08830185.2024.2321901","article-title":"Th17 cells: A new target in kidney disease research","volume":"43","author":"Zhang","year":"2024","journal-title":"Int. Rev. Immunol."},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.29219\/fnr.v66.8948","article-title":"Quercetin effectively improves LPS-induced intestinal inflammation, pyroptosis, and disruption of the barrier function through the TLR4\/NF-\u03baB\/NLRP3 signaling pathway in vivo and in vitro","volume":"66","author":"Zhang","year":"2022","journal-title":"Food Nutr. Res."},{"key":"B120","doi-asserted-by":"publisher","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":"2022","journal-title":"Front. Pharmacol."},{"key":"B121","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41467-023-44373-x","article-title":"Gut microbiota facilitate chronic spontaneous urticaria","volume":"15","author":"Zhu","year":"2024","journal-title":"Nat. Commun."},{"key":"B122","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1161\/circresaha.122.321749","article-title":"Innate immunity system in patients with cardiovascular and kidney disease","volume":"132","author":"Zoccali","year":"2023","journal-title":"Circ. Res."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1811786\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:39:21Z","timestamp":1779255561000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1811786\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":122,"alternative-id":["10.3389\/fcimb.2026.1811786"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1811786","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"article-number":"1811786"}}