{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T00:15:47Z","timestamp":1793578547641,"version":"4.5.0"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"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. Immunol."],"abstract":"<jats:p>The progression of Chronic Kidney Disease (CKD) is governed by a pathogenic interplay between the host and the gut microbiota, a relationship encapsulated in the gut-kidney axis. This review synthesizes current knowledge on gut microbial alterations, metabolic reprogramming, and immunopathological mechanisms in CKD. Patients with CKD exhibit reduced microbial diversity, depletion of beneficial butyrate\u2212producing bacteria, and enrichment of pathogenic taxa harboring urease, tryptophanase, and tyrosine phenol\u2212lyase. These compositional shifts drive overproduction of protein\u2212bound uremic toxins (indoxyl sulfate, p\u2212cresyl sulfate, phenylacetylglutamine) and non\u2212protein\u2212bound toxins (trimethylamine N\u2212oxide) via tryptophan, tyrosine, and arginine metabolic pathways. Mechanistically, uremic toxins disrupt intestinal tight junctions, promote endotoxin translocation, and trigger systemic inflammation. At the renal level, they induce direct cytotoxicity, endothelial dysfunction, oxidative stress (via NF\u2212\u03baB, MAPK, AhR signaling), and activation of both innate and adaptive immune responses. These processes converge to promote epithelial\u2013mesenchymal transition, myofibroblast activation and renal fibrosis. Importantly, these elements form a self-sustaining vicious cycle: declining renal function leads to toxin buildup, which further accelerates CKD progression and its systemic complications. By comprehensively elucidating this bidirectional communication, we underscore the promising therapeutic strategy of suppressing uremic toxin generation or replenishing beneficial metabolites such as short\u2212chain fatty acids to disrupt this cycle, thereby opening avenues for decelerating the advancement of CKD.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1801912","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:46:09Z","timestamp":1778215569000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["The gut-kidney axis in chronic kidney disease: a vicious cycle of microbial dysbiosis and uremic toxin accumulation"],"prefix":"10.3389","volume":"17","author":[{"given":"Ruohan","family":"Guan","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Zhejiang Chinese Medical 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