[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-344663-105":59,"doc-detail-344663-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","dysbiosis-mediated-regulation-of-stem-cells-the-first-hit-for-cancer-generation","Dysbiosis-Mediated Regulation of Stem Cells: the First Hit for Cancer Generation","","Human microbiota, a complex consortium of microorganisms co-evolved with the host, profoundly influences tissue development, immune regulation, and disease progression. Growing evidence shows that microbial metabolites and signaling molecules modulate key stem cell pathways—such as Hedgehog, Wnt/β-catenin, and Notch—thereby reprogramming stem cell fate toward tumor-suppressive or tumor-promoting outcomes. Specific taxa in oral, intestinal, and urogenital niches relate to cancer initiation and recurrence, while clinical findings indicate microbiota composition shapes infection dynamics. These insights support microbiota-targeted interventions to improve cancer and infectious disease management.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/dysbiosis-mediated-regulation-of-stem-cells-the-first-hit-for-cancer-generation/344663/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/dysbiosis-mediated-regulation-of-stem-cells-the-first-hit-for-cancer-generation/344663.png","ImageObject",300,407,{"name":92,"@type":93},"Himbo","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does dysbiosis influence cancer susceptibility before genetic damage occurs?","Question",{"text":112,"@type":113},"Dysbiosis is described as an upstream, ongoing process that disrupts epithelial homeostasis by impairing stem-cell quiescence, niche signaling, and regenerative fidelity. This disruption lowers the threshold for later genetic or epigenetic alterations.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which stem-cell signaling pathways are regulated by microbial metabolites and signals?",{"text":117,"@type":113},"The article highlights modulation of Hedgehog, Wnt/β-catenin, and Notch pathways. It also notes apoptosis-related cascades involving STAT1–3, SMAC/DIABLO, and HIF-1.",{"name":119,"@type":110,"acceptedAnswer":120},"How can microbiota composition affect infection dynamics according to the document?",{"text":121,"@type":113},"Clinical studies indicate that microbiota composition influences infection dynamics, including that bacterial isolates from symptomatic urinary tract infections inhibit commensal growth more strongly than the reverse. Gram-positive and Gram-negative strains show distinct interaction profiles.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},344663,1790176883,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},687197100911,"https://ap-avatar.wpscdn.com/avatar/a000239b6f1da00475?x-image-process=image/resize,m_fixed,w_180,h_180&k=1785132997149421697","Review  \nDysbiosis-Mediated Regulation of Stem Cells the First Hit for Cancer Generation  \nCiro Gargiulo-Isacco 1,*, Van Hung Pham 2, Kieu C. D. Nguyen 1, Toai C. Tran 3, Sergey K. Aityan 4, Raffaele Del Prete 1, Emilio Jirillo 1 and Luigi Santacroce 1  \nAcademic Editor: Alfredo Miccheli  \nReceived: 20 November 2025  \nRevised: 31 December 2025  \nAccepted: 5 January 2026  \nPublished: 8 January 2026  \nCopyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Department of Interdisciplinary Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; [drkieukaren@gmail.com](drkieukaren@gmail.com) (K.C.D.N.); [raffaele.delprete@uniba.it](raffaele.delprete@uniba.it) (R.D.P.); [emilio.jirillo@uniba.it](emilio.jirillo@uniba.it) (E.J.); [luigi.santacroce@uniba.it](luigi.santacroce@uniba.it) (L.S.)  \n2 Viet Nam Research and Development Institute of Clinical Microbiology, Ho Chi Minh City 756000, Vietnam; [phhvan.nkbiotek@gmail.com](phhvan.nkbiotek@gmail.com)  \n3 Basic Medical Sciences Faculty, Pham Ngoc Thach University of Medicine, Ho Chi Minh City 740500, Vietnam  \n4 Department of Multidisciplinary Engineering, Northeastern University, Oakland Campus, Oakland, CA 94613-1301, USA; [s.aityan@northeastern.edu](s.aityan@northeastern.edu)  \n* Correspondence: [drciroisacco@gmail.com](drciroisacco@gmail.com)  \nAbstract  \nHuman microbiota, a complex consortium of microorganisms co-evolved with the host, profoundly influences tissue development, immune regulation, and disease progression. Growing evidence shows that microbial metabolites and signaling molecules modulate key stem cell pathways—such as Hedgehog, Wnt/β-catenin, and Notch—thereby reprogramming stem cell fate toward tumor-suppressive or tumor-promoting outcomes. Specific taxa within oral, intestinal, and urogenital niches have been linked to cancer initiation, therapy resistance, and recurrence. In parallel, clinical studies reveal that microbiota composition affects infection dynamics: bacterial isolates from symptomatic urinary tract infections inhibit commensal growth more strongly than the reverse, with Gram-positive and Gram-negative strains displaying distinct interaction profiles. Collectively, these findings highlight microbiota’s dual role in regulating cellular plasticity and pathogenicity. Elucidating host– microbe and microbe–microbe mechanisms may guide microbiota-targeted interventions to improve cancer and infectious disease management.  \nKeywords: cancer; dysbiosis; microbiota; hormones; cancer stem cells; immunity; β-glucuronidase (GUS)  \n1. Microbiota, Age and Cellular Reprogramming in Health and Disease  \nIntroduction  \nDespite the central role of genetic mutations in classical models of carcinogenesis, these frameworks remain mostly incomplete. They do not fully explain the spatially and temporally extensive tissue vulnerability observed prior to malignant transformation, nordo they account for why genetically similar epithelia often exhibit highly divergent cancer risk [1] . These limitations suggest the existence of upstream, non-genetic determinants that shape the carcinogenic landscape before irreversible genomic alterations occur [1] .  \nAccumulating evidence supports a model in which aging-related factors (including stem cell dysfunction, hormonal imbalance, and microbial dysbiosis) play a critical upstream role in cancer susceptibility [2] . Aging, combined with microbial dysbiosis, represents a persistent and hushed perturbation of the mucosal microenvironment, capable of  \ndurably altering metabolite availability, microbial enzymatic activity, immune tone, and epithelial signaling [3] . As such, dysbiosis is uniquely positioned to act upstream of subsequent genetic damage, reshaping tissue homeostasis long before malignant transformation becomes de","cbCaikXakMTwpMdh","https://ap.wps.com/l/cbCaikXakMTwpMdh","pdf",1596310,"English","# Microbiota, Age and Cellular Reprogramming in Health and Disease\n# Introduction","[{\"question\":\"How does dysbiosis influence cancer susceptibility before genetic damage occurs?\",\"answer\":\"Dysbiosis is described as an upstream, ongoing process that disrupts epithelial homeostasis by impairing stem-cell quiescence, niche signaling, and regenerative fidelity. This disruption lowers the threshold for later genetic or epigenetic alterations.\"},{\"question\":\"Which stem-cell signaling pathways are regulated by microbial metabolites and signals?\",\"answer\":\"The article highlights modulation of Hedgehog, Wnt/β-catenin, and Notch pathways. It also notes apoptosis-related cascades involving STAT1–3, SMAC/DIABLO, and HIF-1.\"},{\"question\":\"How can microbiota composition affect infection dynamics according to the document?\",\"answer\":\"Clinical studies indicate that microbiota composition influences infection dynamics, including that bacterial isolates from symptomatic urinary tract infections inhibit commensal growth more strongly than the reverse. Gram-positive and Gram-negative strains show distinct interaction profiles.\"}]","Dysbiosis-Mediated Regulation of Stem Cells: the First Hit for Cancer Generation | PDF",1790054790,48]