{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T02:48:32Z","timestamp":1787971712094,"version":"build-2784847793"},"reference-count":43,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Benign prostatic hyperplasia (BPH), a prevalent age\u2010related condition in men, is increasingly linked to metabolic syndrome (MetS) and gut microbiota dysbiosis. This study reveals how Firmicutes\u2010dominant microbial imbalance drives BPH progression via IGF\u20101 signaling and identifies the green tea polyphenol epigallocatechin\u20103\u2010gallate (EGCG) as a dual\u2010action therapeutic. Using MetS\u2010BPH mouse models and human prostate cell lines, we demonstrated that BPH\u2010associated gut microbiota\u2014particularly elevated Firmicutes and an increased Firmicutes\/Bacteroidetes ratio\u2014promotes prostate hyperplasia by upregulating IGF\u20101. Both BPH mice and recipient mice transplanted with BPH microbiota showed elevated serum and prostate IGF\u20101 levels, mirroring findings in human BPH patients. Mechanistically, IGF\u20101 stimulated prostate cell proliferation (RWPE\u20101\/WPMY\u20101) and suppressed apoptosis via PI3K\/AKT\/mTOR activation, while the IGF\u20101 antagonist Linsitinib reversed these effects. EGCG emerged as a potent modulator of this gut\u2010prostate axis: it selectively reduced Firmicutes overgrowth in BPH mice, normalized IGF\u20101 levels, and inhibited downstream PI3K\/AKT\/mTOR signaling. In fecal microbiota transplantation experiments, EGCG counteracted IGF\u20101\u2010driven prostate enlargement and microbial dysbiosis, underscoring its dual role in rebalancing gut flora and blocking growth factor pathways. Our findings position EGCG as a promising intervention for MetS\u2010associated BPH, simultaneously targeting microbial dysbiosis and IGF\u20101 signaling. This study not only elucidates the Firmicutes\u2013IGF\u20101 axis in BPH pathogenesis but also highlights the therapeutic potential of dietary polyphenols in metabolic urological disorders.<\/jats:p>","DOI":"10.1002\/cbin.70032","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T08:34:20Z","timestamp":1750754060000},"page":"952-964","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Epigallocatechin\u20103\u2010Gallate Attenuates Benign Prostatic Hyperplasia Development via Regulating Firmicutes to Inhibit Gastric Secretion of Insulin\u2010Like Growth Factor\u20101"],"prefix":"10.1002","volume":"49","author":[{"given":"Tianye","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Emergency Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YiQun","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Urology and Andrology Gongli Hospital of Shanghai Pudong New Area Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology and Andrology Gongli Hospital of Shanghai Pudong New Area Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8269-1488","authenticated-orcid":false,"given":"Meng","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Urology Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40842-024-00187-4"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24656"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2016.06.015"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114524002356"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175762"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i43.16079"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2024.123192"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-015-2061-5"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2011.139"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1393641"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.615928"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2011.05.008"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0000000000000149"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms12112333"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst0300317"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.02.006"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.13645"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.10087"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-2274"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.endonu.2016.07.008"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2021.108910"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-7075-9-11"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2006.05.040"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/d3fo03107a"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20506"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18309"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24131"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/3079148"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00061"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2019.03.017"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498250600621627"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2009.167"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-10-0331"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.66822"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2014.01.006"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.2007.s26"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-18-0422"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.72157"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-018-1826-9"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/08923973.2024.2384899"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12590"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113708"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods13081232"}],"container-title":["Cell Biology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbin.70032","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T10:24:07Z","timestamp":1752575047000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbin.70032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,24]]},"references-count":43,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/cbin.70032"],"URL":"https:\/\/doi.org\/10.1002\/cbin.70032","archive":["Portico"],"relation":{},"ISSN":["1065-6995","1095-8355"],"issn-type":[{"value":"1065-6995","type":"print"},{"value":"1095-8355","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,24]]},"assertion":[{"value":"2025-02-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}