{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T06:10:23Z","timestamp":1783923023974,"version":"3.55.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2024AFD316"],"award-info":[{"award-number":["2024AFD316"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2026AFC0920"],"award-info":[{"award-number":["2026AFC0920"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic kidney disease (CKD) is a progressive disorder characterized by persistent renal dysfunction, inflammation, and fibrosis. Sirtuin 3 (SIRT3), a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase, has been implicated in the regulation of mitochondrial homeostasis, oxidative stress, and renal injury. However, whether SIRT3 participates in CKD progression through gut\u2013kidney axis-related alterations remains unclear. This study investigated the role of SIRT3 in renal injury, fibrosis, intestinal barrier dysfunction, and gut microbiota dysbiosis in CKD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An adenine-induced CKD model was established in global SIRT3 knockout mice. Renal function, inflammatory markers, histopathological injury, fibrosis-related proteins, colonic injury, intestinal barrier-related proteins, and gut microbial composition were evaluated. In parallel, human proximal tubular epithelial HK-2 cells were treated with transforming growth factor-\u03b21 (TGF-\u03b21), with or without the SIRT3 inhibitor 3-TYP, to assess profibrotic responses and apoptosis\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Gut microbiota alterations were analyzed by 16S rRNA gene sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SIRT3 deficiency alone did not produce overt abnormalities under basal conditions, but significantly aggravated adenine-induced renal dysfunction, inflammatory responses, tubulointerstitial fibrosis, and structural kidney injury. In CKD mice, SIRT3 deficiency also worsened colonic injury, reduced the expression of zonula occludens-1 and occludin, and was associated with more pronounced gut microbiota dysbiosis.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , inhibition of SIRT3 further enhanced TGF-\u03b21-induced profibrotic protein expression and apoptosis in HK-2 cells. Correlation analysis further suggested significant associations between specific microbial taxa and indices of renal fibrosis and renal dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings indicate that SIRT3 exerts a protective role in CKD progression. Loss of SIRT3 aggravates CKD progression not only by worsening local renal injury, but also in association with gut\u2013kidney axis-related abnormalities. Collectively, our results suggest that SIRT3 may represent a potential therapeutic target for CKD and provide a basis for further mechanistic investigation of its role in renal fibrosis and gut\u2013kidney axis dysfunction<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1851246","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:33:53Z","timestamp":1783920833000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["SIRT3 deficiency aggravates renal injury and fibrosis in chronic kidney disease and is associated with intestinal barrier dysfunction and gut microbiota dysbiosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhili","family":"Xiong","sequence":"first","affiliation":[{"name":"Hubei Provincial Hospital of Traditional Chinese Medicine","place":["Wuhan, China"]},{"name":"Affiliated Hospital of Hubei University of Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Research Institute of Traditional Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Key Laboratory of Theory and Application Research of Liver and Kidney in Traditional Chinese Medicine","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Qian","sequence":"additional","affiliation":[{"name":"Hubei Provincial Hospital of Traditional Chinese Medicine","place":["Wuhan, China"]},{"name":"Affiliated Hospital of Hubei University of Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Research Institute of Traditional Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Key Laboratory of Theory and Application Research of Liver and Kidney in Traditional Chinese Medicine","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hubei Provincial Hospital of Traditional Chinese Medicine","place":["Wuhan, China"]},{"name":"Affiliated Hospital of Hubei University of Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Research Institute of Traditional Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Key Laboratory of Theory and Application Research of Liver and Kidney in Traditional Chinese Medicine","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei Provincial Hospital of Traditional Chinese Medicine","place":["Wuhan, China"]},{"name":"Affiliated Hospital of Hubei University of Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Research Institute of Traditional Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Key Laboratory of Theory and Application Research of Liver and Kidney in Traditional Chinese Medicine","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdi","family":"Cui","sequence":"additional","affiliation":[{"name":"Hubei Provincial Hospital of Traditional Chinese Medicine","place":["Wuhan, China"]},{"name":"Affiliated Hospital of Hubei University of Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Research Institute of Traditional Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Key Laboratory of Theory and Application Research of Liver and Kidney in Traditional Chinese Medicine","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiying","family":"Xiong","sequence":"additional","affiliation":[{"name":"Hubei Provincial Hospital of Traditional Chinese Medicine","place":["Wuhan, China"]},{"name":"Affiliated Hospital of Hubei University of Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Research Institute of Traditional Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Key Laboratory of Theory and Application Research of Liver and Kidney in Traditional Chinese Medicine","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Tian","sequence":"additional","affiliation":[{"name":"Hubei Provincial Hospital of Traditional Chinese Medicine","place":["Wuhan, China"]},{"name":"Affiliated Hospital of Hubei University of Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Research Institute of Traditional Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Key Laboratory of Theory and Application Research of Liver and Kidney in Traditional Chinese Medicine","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Guan","sequence":"additional","affiliation":[{"name":"Hubei Provincial Hospital of Traditional Chinese Medicine","place":["Wuhan, China"]},{"name":"Affiliated Hospital of Hubei University of Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Research Institute of Traditional Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Key Laboratory of Theory and Application Research of Liver and Kidney in Traditional Chinese Medicine","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.3390\/ph18111668","article-title":"The role of sirt3 in kidney health and disease","volume":"18","author":"Azzouz","year":"2025","journal-title":"Pharmaceuticals"},{"key":"B2","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1093\/bib\/bbz155","article-title":"Current challenges and best-practice protocols for microbiome analysis","volume":"22","author":"Bharti","year":"2019","journal-title":"Brief. Bioinformatics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.3390\/ijms22031233","article-title":"Intestinal SIRT1 deficiency-related intestinal inflammation and dysbiosis aggravate TNF\u03b1-mediated renal dysfunction in cirrhotic ascitic mice","volume":"22","author":"Chou","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"157724","DOI":"10.1016\/j.phymed.2025.157724","article-title":"Dahuang Gancao decoction suppresses ferroptosis via SIRT3-mediated NRF2 deacetylation in acute kidney injury","volume":"150","author":"Cui","year":"2026","journal-title":"Phytomedicine"},{"key":"B5","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/s41581-024-00820-6","article-title":"Chronic kidney disease and the global public health agenda: an international consensus","volume":"20","author":"Francis","year":"2024","journal-title":"Nat. Rev. Nephrol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"5457","DOI":"10.1038\/s41598-025-90306-7","article-title":"Investigating the role of gut microbiota in diabetic nephropathy through plasma proteome mediated analysis","volume":"15","author":"Fu","year":"2025","journal-title":"Sci. Rep."},{"key":"B7","doi-asserted-by":"publisher","first-page":"103660","DOI":"10.1016\/j.sjbs.2023.103660","article-title":"A novel model of adenine-induced chronic kidney disease-associated gastrointestinal dysfunction in mice: the gut-kidney axis","volume":"30","author":"Hayeeawaema","year":"2023","journal-title":"Saudi J. Biol. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1172\/JCI41563","article-title":"Sirt1 activation protects the mouse renal medulla from oxidative injury","volume":"120","author":"He","year":"2010","journal-title":"J. Clin. Invest."},{"key":"B9","doi-asserted-by":"publisher","first-page":"S117","DOI":"10.1016\/j.kint.2023.10.018","article-title":"Clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"105","year":"2024","journal-title":"Kidney Int."},{"key":"B10","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/s41581-022-00647-z","article-title":"Gut microbiome studies in CKD: opportunities, pitfalls and therapeutic potential","volume":"19","author":"Krukowski","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1038\/s41564-026-02259-w","article-title":"Host factors dictate gut microbiome alterations in chronic kidney disease more strongly than kidney function","volume":"11","author":"Krukowski","year":"2026","journal-title":"Nat. Microbiol."},{"key":"B12","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":"B13","doi-asserted-by":"publisher","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":"B14","doi-asserted-by":"publisher","first-page":"1298432","DOI":"10.3389\/fmicb.2024.1298432","article-title":"Gut microbiota associations with chronic kidney disease: insights into nutritional and inflammatory parameters","volume":"15","author":"Lazarevic","year":"2024","journal-title":"Front. Microbiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/s41522-025-00772-0","article-title":"Parabacteroides as a promising target for disease intervention: current stage and pending issues","volume":"11","author":"Liu","year":"2025","journal-title":"NPJ Biofilms Microbiomes"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1628488","DOI":"10.3389\/fcimb.2025.1628488","article-title":"Pingwei powder alleviates high-fat diet-induced colonic inflammation by modulating microbial metabolites SCFAs","volume":"15","author":"Liu","year":"2025","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"157412","DOI":"10.1016\/j.phymed.2025.157412","article-title":"Bupi Yishen formula against chronic kidney injury via Akkermansia muciniphila mediated group 3 innate lymphoid cells activation to repair intestinal barrier funciton","volume":"148","author":"Liu","year":"2025","journal-title":"Phytomedicine"},{"key":"B18","doi-asserted-by":"publisher","first-page":"12150","DOI":"10.1038\/s41598-023-39444-4","article-title":"Alterations of gut microbiota in biopsy-proven diabetic nephropathy and a long history of diabetes without kidney damage","volume":"13","author":"Lu","year":"2023","journal-title":"Sci. Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2461","DOI":"10.1016\/S0140-6736(25)01853-7","article-title":"Global, regional, and national burden of chronic kidney disease in adults, 1990\u20132023, and its attributable risk factors: a systematic analysis for the global burden of disease study 2023","volume":"406","author":"Mark","year":"2025","journal-title":"Lancet"},{"key":"B20","doi-asserted-by":"publisher","first-page":"298","DOI":"10.3390\/toxins10070298","article-title":"Intestinal barrier function in chronic kidney disease","volume":"10","author":"Meijers","year":"2018","journal-title":"Toxins"},{"key":"B21","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/s41581-024-00889-z","article-title":"Metabolism at the crossroads of inflammation and fibrosis in chronic kidney disease","volume":"21","author":"Miguel","year":"2025","journal-title":"Nat. Rev. Nephrol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1038\/s41467-022-28034-z","article-title":"Microbiome differential abundance methods produce different results across 38 datasets","volume":"13","author":"Nearing","year":"2022","journal-title":"Nat. Commun."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2992","DOI":"10.3390\/nu15132992","article-title":"NAD+ precursors and intestinal inflammation: therapeutic insights involving gut microbiota","volume":"15","author":"Ni\u00f1o-Narvi\u00f3n","year":"2023","journal-title":"Nutrients"},{"key":"B24","doi-asserted-by":"publisher","first-page":"120577","DOI":"10.1016\/j.jep.2025.120577","article-title":"Huopu Xialing decoction mitigates influenza A-induced pulmonary injury by inhibiting METTL3-Nlrp3(m6A) mediated NLRP3 inflammasome activation","volume":"355","author":"Ou","year":"","journal-title":"J. Ethnopharmacol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"157771","DOI":"10.1016\/j.phymed.2026.157771","article-title":"Plantago asiatica L. extract alleviates hyperuricemia-associated renal injury by modulating gut microbiota to inhibit NLRP3 inflammasome activation","volume":"151","author":"Ou","year":"","journal-title":"Phytomedicine"},{"key":"B26","doi-asserted-by":"publisher","first-page":"105891","DOI":"10.1016\/j.micpath.2022.105891","article-title":"Akkermansia muciniphila ameliorates chronic kidney disease interstitial fibrosis via the gut-renal axis","volume":"174","author":"Pei","year":"2023","journal-title":"Microb. Pathog."},{"key":"B27","doi-asserted-by":"publisher","first-page":"107261","DOI":"10.1016\/j.phrs.2024.107261","article-title":"Sirtuin 3 in renal diseases and aging: from mechanisms to potential therapies","volume":"206","author":"Peng","year":"2024","journal-title":"Pharmacol. Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"235","DOI":"10.3164\/jcbn.23-42","article-title":"Sirtuin 3 ameliorates inflammatory bowel disease via inhibiting intestinal inflammation and oxidative stress","volume":"74","author":"Qin","year":"2024","journal-title":"J. Clin. Biochem. Nutr."},{"key":"B29","doi-asserted-by":"publisher","first-page":"21685","DOI":"10.1038\/s41598-025-05941-x","article-title":"Mendelian randomization study revealed a gut microbiota-immune system-kidney junction axis in chronic kidney disease","volume":"15","author":"Tan","year":"2025","journal-title":"Sci. Rep."},{"key":"B30","doi-asserted-by":"publisher","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":"B31","doi-asserted-by":"publisher","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":"B32","doi-asserted-by":"publisher","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":"B33","doi-asserted-by":"publisher","first-page":"26905","DOI":"10.1038\/s41598-025-06143-1","article-title":"Gavage versus dietary adenine administration is more effective for the female mouse model of chronic kidney disease","volume":"15","author":"Vi\u00f1uela-Berni","year":"2025","journal-title":"Sci. Rep."},{"key":"B34","doi-asserted-by":"publisher","first-page":"790783","DOI":"10.3389\/fmed.2021.790783","article-title":"The human microbiome in chronic kidney disease: a double-edged sword","volume":"8","author":"Wehedy","year":"2021","journal-title":"Front. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1526414","DOI":"10.3389\/fphar.2025.1526414","article-title":"Jingtian granule alleviates adenine-induced renal fibrosis in mice through SIRT3-mediated deacetylation of P53","volume":"16","author":"Xiong","year":"2025","journal-title":"Front. Pharmacol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41420-025-02929-4","article-title":"IL-1 receptor antagonism attenuates renal fibrosis via RNF182-driven MFN2 destabilization and mitochondrial dysfunction","volume":"12","author":"Yang","year":"2025","journal-title":"Cell Death Discov."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2336128","DOI":"10.1080\/0886022X.2024.2336128","article-title":"Adenine-induced animal model of chronic kidney disease: current applications and future perspectives","volume":"46","author":"Yang","year":"2024","journal-title":"Ren. Fail."},{"key":"B38","doi-asserted-by":"publisher","first-page":"102881","DOI":"10.1016\/j.xpro.2024.102881","article-title":"Protocol for induction of human kidney cell fibrosis","volume":"5","author":"Zhang","year":"2024","journal-title":"STAR Protoc."},{"key":"B39","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1038\/s41419-021-04134-4","article-title":"Sirtuin 3 regulates mitochondrial protein acetylation and metabolism in tubular epithelial cells during renal fibrosis","volume":"12","author":"Zhang","year":"2021","journal-title":"Cell Death Dis."},{"key":"B40","doi-asserted-by":"publisher","first-page":"466","DOI":"10.3390\/cells14060466","article-title":"Sirtuins and gut microbiota: dynamics in health and a journey from metabolic dysfunction to hepatocellular carcinoma","volume":"14","author":"Zhra","year":"2025","journal-title":"Cells"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1851246\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:33:55Z","timestamp":1783920835000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1851246\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,13]]},"references-count":40,"alternative-id":["10.3389\/fmicb.2026.1851246"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1851246","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,13]]},"article-number":"1851246"}}