[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-407905-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-407905-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","the-gut-joint-connection-microbiomes-role-in-rheumatic-disease","The Gut-Joint Connection - Microbiome’s Role in Rheumatic Disease","","The human gut microbiome regulates systemic immunity and drives the pathogenesis of rheumatic diseases. Microbial imbalance, or dysbiosis, sustains autoimmunity via the gut-joint axis, with increased intestinal permeability enabling microbial products such as lipopolysaccharide to enter circulation and amplify chronic inflammation. Dysbiosis also disrupts the Th17 versus Treg homeostatic balance, a key hallmark in rheumatoid arthritis, ankylosing spondylitis, and systemic lupus erythematosus.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/the-gut-joint-connection-microbiomes-role-in-rheumatic-disease/407905/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/the-gut-joint-connection-microbiomes-role-in-rheumatic-disease/407905.png","ImageObject",300,407,{"name":42,"@type":43},"Dipper","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-28",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the gut-joint axis in rheumatic disease?","Question",{"text":63,"@type":64},"It describes how gut microbiome dysregulation can influence systemic immunity and contribute to rheumatic disease through interconnected mechanisms such as immune activation and inflammation.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does increased intestinal permeability contribute to autoimmunity?",{"text":68,"@type":64},"Disrupted barrier integrity increases permeability, allowing microbial products like lipopolysaccharide to translocate into systemic circulation and provoke chronic inflammation.",{"name":70,"@type":61,"acceptedAnswer":71},"Why are the Th17 and Treg cells important in these diseases?",{"text":72,"@type":64},"The gut microbiota shapes the balance between pro-inflammatory Th17 cells and immune-tolerating Treg cells; dysbiosis shifts this balance and intensifies autoimmune responses.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},407905,1791157930,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":55,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144,"preview_page_count":4},1374404997633,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","INVITED REVIEW  \nArchives of Rheumatology 2025;40(4):413-421 DOI: 10.5152/ArchRheumatol.2025.25192  \nThe Gut-Joint Connection: Microbiome’s Role in Rheumatic Disease  \nABSTRACT  \nThe human gut microbiome is a pivotal regulator of systemic immunity and a central factor in the pathogenesis of rheumatic diseases. An imbalance in this microbial community, known as “dysbiosis,” can trigger and perpetuate autoimmune responses through the “gut-joint axis.” A key mechanism underpinning this connection is increased intestinal permeability (“leaky gut”), which facilitates the translocation of microbial products like lipopolysaccharide into the systemic circulation, thereby provoking chronic inflammation. Concurrently, dysbiosis disrupts the critical homeostatic balance between pro-inflammatory Th17 cells and regulatory T cells, an immunological hallmark of conditions such as rheumatoid arthritis (RA), ankylosing spondylitis, and systemic lupus erythematosus (SLE) .  \nSpecific microbial signatures, including the expansion of Prevotella copri in RA and Ruminococcus gnavus in SLE, are emerging as potential diagnostic biomarkers. This deeper understanding is paving the way for innovative therapeutic strategies. Interventions aimed at modulating the gut microbiota, such as targeted diets, probiotics, prebiotics and fecal microbiota transplantation, represent a promising frontier for the personalized management of rheumatic diseases. This review explores the foundational mechanisms linking the microbiome to autoimmunity and discusses the clinical potential of harnessing the gut-joint axis to improve patient outcomes.  \nKeywords: Arthritis, autoimmune disease, dysbiosis, gut-joint axis, intestinal permeability, microbiome, rheumatology, Th17, Treg balance  \nIntroduction and Basic Mechanisms  \nThe human body harbors an ecosystem comprising human cells alongside bacteria, archaea, viruses, and fungi, termed the human microbiome.1-3 The majority of the microbial load resides in the large intestine, hosting >1500 species across >50 phyla, with Bacteroidetes and Firmicutes constituting the bulk of adult gut bacteria.1,4 ,5 The microbiota maintains a symbiotic “eubiosis”balance with the host, performing metabolic, protective, and immune-regulatory functions: fermentation of fibers, vitamin synthesis, and short-chain fatty acid (SCFA) production; prevention of pathogen colonization and support of barrier integrity; and education of mucosal immune responses are among the primary ones.1,3,6-8 These mutual interactions have heightened interest in the microbiome’s role in the etiology of autoimmune and rheumatic diseases.1,2,8-13  \nBarrier Integrity and “Leaky Gut”  \nTight junctions in the intestinal epithelium limit passage from the lumen to systemic circulation; disruption of zonulin-mediated regulation increases permeability, allowing microbial products such as lipopolysaccharide (LPS) to leak  \nCopyright@Author(s) -[Available online at archivesof rheumatology.com](Available online at archivesof rheumatology.com). Content of this journal is licensed under a Creative Commons Attribution (CC BY) 4.0 International License.  \nNilay Şahin Ender Salbaş  \nDepartment of Physical Medicine and Rehabilitation, Balıkesir University Faculty of Medicine, Balıkesir, Türkiye  \nCorresponding author: Nilay Şahin  \n􀀍 [dincernilay@yahoo.com](dincernilay@yahoo.com)  \nReceived: October 19, 2025  \nAccepted: October 27, 2025  \nPublication Date: December 1, 2025  \nCite this article as: Şahin N, Salbaş E. The gut-joint connection: Microbiome’s role in rheumatic disease. Arch Rheumatol. 2025;40(4):413-421 .  \n413  \nArchives of Rheumatology 2025;40(4):413-421 Şahin and Salbaş. Gut Microbiome and Rheumatic Disease  \nand elevate tumor necrosis factor-α (TNF-α)/Interleukin-6  \n(IL-6) production via the TLR4–MyD88 pathway, thereby amplifying systemic inflammation.3,9,14-20 In ankylosing spondylitis (AS), epithelial and vascular barrier disruption with elevated zonulin levels has bee","cbCaibQfSeyc047G","https://ap.wps.com/l/cbCaibQfSeyc047G","pdf",906771,"English","# Introduction and Basic Mechanisms\n# Barrier Integrity and “Leaky Gut”\n# Helper T17/Regulatory T Balance\n# Microbial Metabolites\n# Main Points","[{\"question\":\"What is the gut-joint axis in rheumatic disease?\",\"answer\":\"It describes how gut microbiome dysregulation can influence systemic immunity and contribute to rheumatic disease through interconnected mechanisms such as immune activation and inflammation.\"},{\"question\":\"How does increased intestinal permeability contribute to autoimmunity?\",\"answer\":\"Disrupted barrier integrity increases permeability, allowing microbial products like lipopolysaccharide to translocate into systemic circulation and provoke chronic inflammation.\"},{\"question\":\"Why are the Th17 and Treg cells important in these diseases?\",\"answer\":\"The gut microbiota shapes the balance between pro-inflammatory Th17 cells and immune-tolerating Treg cells; dysbiosis shifts this balance and intensifies autoimmune responses.\"}]","The Gut-Joint Connection - Microbiome’s Role in Rheumatic Disease | PDF",1790576838,23]