[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-449491-105":59,"doc-detail-449491-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","response-to-letter-regarding-beyond-inflammation-what-drives-the-self-perpetuating-cycle-of-fibrosis-in-ibd","Response to letter regarding “beyond inflammation: what drives the self-perpetuating cycle of fibrosis in IBD?”","","Response letter to an editor addressing critiques of a recent review on intestinal fibrosis in inflammatory bowel disease (IBD). The author explains the “self-perpetuating fibrosis” concept as a framework complementing inflammation’s initiating role, emphasizing why anti-inflammatory therapy alone may not stop established fibrotic progression. The letter highlights mechanisms sustaining fibrosis beyond inflammation, including genetic predisposition, matrix stiffness-driven fibroblast activation, and metabolic reprogramming.",{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/response-to-letter-regarding-beyond-inflammation-what-drives-the-self-perpetuating-cycle-of-fibrosis-in-ibd/449491/",{"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/response-to-letter-regarding-beyond-inflammation-what-drives-the-self-perpetuating-cycle-of-fibrosis-in-ibd/449491.png","ImageObject",300,407,{"name":92,"@type":93},"pop out","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-06","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the purpose of the proposed “self-perpetuating fibrosis” framework in IBD?","Question",{"text":112,"@type":113},"It provides a coherent explanatory model for persistent clinical fibrosis in advanced disease, clarifying why anti-inflammatory strategies alone may not fully halt or reverse established fibrotic progression.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which mechanisms are highlighted as sustaining fibrosis beyond inflammatory control?",{"text":117,"@type":113},"The response cites genetic predisposition, matrix stiffness-mediated fibroblast activation, and metabolic reprogramming as drivers that can operate independently of inflammation.",{"name":119,"@type":110,"acceptedAnswer":120},"Why are non-invasive biomarkers a critical unmet need according to the letter?",{"text":121,"@type":113},"Current non-invasive biomarkers cannot reliably distinguish inflammatory from fibrotic strictures, limiting patient stratification and evaluation of anti-fibrotic therapies in clinical trials.","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},449491,1790999663,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":14,"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":24,"preview_page_count":4},962090760408,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","AnnAls of Medicine  \n2026, Vol. 58, no. 1, 2610054  \n[https://doi.org/10.1080/07853890.2025.2610054](https://doi.org/10.1080/07853890.2025.2610054)  \nGastroenteroloGy    \nResponse to letter regarding “beyond inflammation: what drives the self-perpetuating cycle of fibrosis in IBD?”  \nDear editor  \nWe sincerely thank the reader for their thoughtful engagement and constructive critique of our recent review [1,2] . the issues raised resonate deeply with ongoing debates in the field of intestinal fibrosis, reflecting the dynamic and evolving understanding of fibrogenesis in inflammatory bowel disease (IBD) . the conceptualization of a ‘self-perpetuating fibrosis’ framework is not intended to diminish the well-established initiating role of inflammation or to dismiss the potential reversibility of early fibrotic changes, which remains an important area of therapeutic opportunity. Instead, this framework seeks to provide a coherent explanatory model for the persistent clinical challenge observed in advanced disease: namely, why anti-inflammatory strategies alone cannot completely halt or reverse established fibrotic progression.  \nBy elucidating the mechanisms that sustain fibrosis beyond inflammatory control-such as genetic predisposition, matrix stiffness-mediated fibroblast activation, and metabolic reprogramming – this model aims to shift the therapeutic paradigm toward identifying and targeting fibrosis-specific pathways that operate independently of inflammation. We fully acknowledge the critical gap in currently available non-invasive biomarkers capable of reliably distinguishing inflammatory from fibrotic strictures, which undeniably hinders both accurate patient stratification and the evaluation of anti-fibrotic therapies in clinical trials. the development and validation of such biomarkers-whether based on imaging, circulating proteins, or transcriptomic signatures-remain an urgent priority to enable precise monitoring of fibrotic activity and therapeutic response. In parallel, we concur that robust longitudinal studies, integrating multi-omics profiling, advanced imaging modalities, and serial biomarker assessment, are essential to validate and stratify fibrotic progression inpatients. It is through such rigorous, interdisciplinary, and collaborative investigation that we can move beyond conceptual frameworks toward actionable clinical strategies, ultimately translating mechanistic insights into meaningful therapeutic outcomes for patients burdened by IBD-related fibrosis. We thank the commentator again for their insightful and substantive contributions, which significantly enrich this critical scientific dialogue.  \nAcknowledgments  \nshiyu Xiao: Conceptualization, supervision, writing – original draft, review and editing.  \nAuthor contributions  \nCredit: Shiyu Xiao: Conceptualization, Funding acquisition, supervision, Writing – original draft, Writing – review & editing.  \nDisclosure statement  \nno potential conflict of interest was reported by the author(s) .  \nData availability statement  \nData sharing is not applicable to this article as no data were created or analyzed in this study.  \nFunding  \nthis study was supported by sichuan science and technology Program [2024nsFsC1687] .  \n2  s. XIao  \nORCID  \nshiyu Xiao  [http://orcid.org/0000-0002-461](http://orcid.org/0000-0002-461)1-1457  \nReferences  \n[1] Wei y, Zhou Z, Xiao s. Beyond inflammation: what drives the self-perpetuating cycle of fibrosis in IBD? ann Med. 2025;57(1):2581923 . doi: 10. 1080/07853890 .2025.2581923.  \n[2] Huang D, shi r, lu y, et al. regarding: ‘beyond inflammation: what drives the self-perpetuating cycle of fibrosis in IBD? ann Med. 2025;57(1):2597689 . doi: 10. 1080/07853890 .2025.2597689.  \nshiyu Xiao   \nDepartment of Gastroenterology, Clinical Immunology Translation Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China  \n ","cbCaibY898QOBgOr","https://ap.wps.com/l/cbCaibY898QOBgOr","pdf",187882,"English","# Response to letter\n## Acknowledgments\n## Author contributions\n## Disclosure statement\n## Data availability statement\n## Funding\n## References","[{\"question\":\"What is the purpose of the proposed “self-perpetuating fibrosis” framework in IBD?\",\"answer\":\"It provides a coherent explanatory model for persistent clinical fibrosis in advanced disease, clarifying why anti-inflammatory strategies alone may not fully halt or reverse established fibrotic progression.\"},{\"question\":\"Which mechanisms are highlighted as sustaining fibrosis beyond inflammatory control?\",\"answer\":\"The response cites genetic predisposition, matrix stiffness-mediated fibroblast activation, and metabolic reprogramming as drivers that can operate independently of inflammation.\"},{\"question\":\"Why are non-invasive biomarkers a critical unmet need according to the letter?\",\"answer\":\"Current non-invasive biomarkers cannot reliably distinguish inflammatory from fibrotic strictures, limiting patient stratification and evaluation of anti-fibrotic therapies in clinical trials.\"}]","Response to letter regarding “beyond inflammation: what drives the self-perpetuating cycle of fibrosis in IBD?” | PDF",1790730342]