{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:48:50Z","timestamp":1791607730409,"version":"4.3.4"},"reference-count":85,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:00:00Z","timestamp":1780790400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Comprehensive Physiology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Chronic kidney disease (CKD) remains a major global health burden despite advances in conventional therapies. This review synthesizes current clinical and experimental evidence on the bidirectional relationship between CKD and gut microbial dysbiosis, emphasizing mechanisms, measurable outcomes, and therapeutic interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A narrative review of recent clinical and experimental studies was conducted to explore alterations in gut microbial composition, generation of uremic toxins, and the impact of CKD therapies on microbial balance. Emerging microbiota\u2010targeted interventions were also examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Studies consistently report reduced microbial diversity, loss of short\u2010chain fatty acid (SCFA)\u2013producing taxa, and enrichment of proteolytic, toxin\u2010producing bacteria in CKD. Gut\u2010derived metabolites such as indoxyl sulfate (IS), p\u2010cresyl sulfate (pCS), and trimethylamine N\u2010oxide (TMAO) are linked to oxidative stress, RAAS activation, and fibrogenesis. In human trials, microbiota\u2010directed therapies show modest biochemical benefits: a meta\u2010analysis of 21 randomized studies reported mean reductions in serum BUN (8.5\u2009mg\/dL) and CRP (1.4\u2009mg\/L) with probiotic or synbiotic supplementation, while inulin (10\u2009g\/day) in stage 3\u20134 CKD reduced serum pCS by 25% and increased fecal butyrate by 40%. However, most mechanistic data derive from animal and in\u00a0vitro models, and human evidence remains heterogeneous and underpowered. Stage\u2010specific differences are evident\u2014early CKD shows subtler dysbiosis, while advanced CKD and dialysis populations exhibit profound microbial shifts and variable responsiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The gut microbiota is a promising, modifiable contributor to CKD pathophysiology. Stage\u2010stratified longitudinal studies are needed to establish causality and therapeutic efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cph4.70192","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T06:08:16Z","timestamp":1780898896000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic Kidney Disease and the Gut Microbiota: An Expanding Confluence in the Development of the Disease"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5807-3033","authenticated-orcid":false,"given":"Muhammad","family":"Ahsan","sequence":"first","affiliation":[{"name":"Jinnah Sindh Medical University  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suheera","family":"Afzoon","sequence":"additional","affiliation":[{"name":"Jinnah Sindh Medical University  Karachi 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