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This study compares patients with severe irAEs versus mild or none, identifying multi-kingdom gut microbiota, fungi, and metabolite signatures. Using metagenomic, ITS2, and metabolomic datasets from 168 advanced patients, severe irAEs associate with longer overall survival, compositional shifts, and a predictive model achieving high discrimination accuracy, highlighting microbiota–fungi–metabolite interaction changes for risk prediction and prognosis.",{"@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/gut-microbiota-and-metabolite-signatures-predict-severe-immune-related-adverse-events-in-advanced-hepatobiliary-cancers/372029/",{"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/gut-microbiota-and-metabolite-signatures-predict-severe-immune-related-adverse-events-in-advanced-hepatobiliary-cancers/372029.png","ImageObject",300,407,{"name":92,"@type":93},"MrHarris58","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-23",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 was the main objective of the study?","Question",{"text":112,"@type":113},"To identify signatures of gut microbiota, fungi, and metabolites associated with severe irAEs in advanced hepatobiliary cancers, compared with mild or no irAEs.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were patients grouped in the analysis?",{"text":117,"@type":113},"Patients with advanced hepatobiliary cancers were enrolled and categorized as having severe irAEs, mild irAEs, or no irAEs, with train and test sets used for model development and evaluation.",{"name":119,"@type":110,"acceptedAnswer":120},"What predictors did the study propose for severe irAEs?",{"text":121,"@type":113},"A predictive model based on four bacterial and six metabolite features simultaneously discriminated severe irAEs from mild and no irAEs, suggesting gut microbiota- and/or metabolite-based algorithms for prediction and prognostic markers.","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},372029,1790330680,{"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":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},687212988360,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Journal of Advanced Research 83 (2026) 775–787  \nContents lists available at ScienceDirect  \nJournal of Advanced Research  \njournal [homepage: www. elsevier. com/locate/jare](homepage: www. elsevier. com/locate/jare)  \n| Gut microbiota and metabolite signatures predict severe\u003Cbr>immune-related adverse events in advanced hepatobiliary cancers |  | |\n| --- | --- | --- |\n| Chengpei Zhu a,b, 1, Dongya Zhang c, 1, Yunchao Wang a,d, 1, Chenchen Zhang c, 1, Shanshan Wang a,\u003Cbr>Jingnan Xue a, Zhou Lan c, Ziyu Xun a, Longhao Zhang a, Jiashuo Chao a, Yajun Liang c, Wenbin Xue c, Zilun Pu c, Taifeng Zhu a, Cong Ning a, Xinting Sang a, Hanping Wang a,e,⁎⁎, Xianzhi Jiang c,⁎, Xiaobo Yang a,⁎, Haitao Zhao a,⁎\u003Cbr>a Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China\u003Cbr>b Department of General Surgery Center, Beijing YouAn Hospital, Clinical Center for Liver Cancer, Capital Medical University, Beijing, China c Microbiome Research Center, Moon (Guangzhou) Biotech Ltd., Guangzhou, China\u003Cbr>d Organ Transplantation Center, The First Affiliated Hospital of Shandong First Medical University, Jinan, China\u003Cbr>e Division of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China |  |  |\n| h i g h l i g h t s\u003Cbr>• Patients with severe irAEs showed differences in bacterial and metabolite composition.\u003Cbr>• Severe irAEs associated with significantly longer progression-free/ overall survival.\u003Cbr>• Predictive model simultaneously discriminated irAE-Severe from irAEMild and irAE-No.\u003Cbr>• Gut microbiota-and/or metabolitebased algorithms could predict severe irAE.\u003Cbr>• The research holds promise for offering more accurate predictions and intervention strategies for clinical practice and patient management. | g r a p h i c a l a b s t r a c t\u003Cbr>|  |\n\na r t i c l e i n f o  \nArticle history:  \nReceived 14 September 2024 Revised 14 July 2025  \nAccepted 11 August 2025  \nAvailable online 12 August 2025  \nKeywords:  \nImmune-related adverse event Gut microbiota  \na b s t r a c t  \nIntroduction: Immune checkpoint inhibition (ICI) has proven to be a major breakthrough in hepatobiliary cancers treatment. However, immune-related adverse events (irAEs) remain a major concern. The gut microbiome has been implicated in ICI efficacy; however, specific alterations in the multi-kingdom gut microbiota associated with severe irAEs are not well understood.  \nObjectives: We aimed to identify the signatures of gut microbiota, fungi, and metabolites in patients with advanced hepatobiliary cancers with severe irAEs compared to those in patients experiencing mild or no irAEs. Methods: We enrolled 168 patients with advanced hepatobiliary cancers between June 2018 and June 2022 (72 in the train set, 31 in test set 1, and 65 in test set 2). Multi-kingdom microbiota profiles were investigated  \n⁎ Corresponding authors.  \n⁎⁎ Corresponding author at: Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China.  \nE-mail [addresses:](addresses: wanghp@pumch.cn)[ wanghp@pumch.cn](addresses: wanghp@pumch.cn) (H. Wang), [jxz@moonbio.com](jxz@moonbio.com) (X. Jiang), [yangxiaobo67@pumch.cn](yangxiaobo67@pumch.cn) (X. Yang), [zhaoht@pumch.cn](zhaoht@pumch.cn) (H. Zhao).  \n1 These authors contributed equally.  \n[https://doi.org/10.1016/j.jare.2025.08.016](https://doi.org/10.1016/j.jare.2025.08.016)  \n2090-1232/© 2025 The Author(s). Published by Elsevier B.V. on behalf of Cairo University.  \nThis is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/license","cbCaip7E0XXMjk9F","https://ap.wps.com/l/cbCaip7E0XXMjk9F","pdf",7750218,13,"English","# Introduction\n# Objectives\n# Methods\n# Results\n# Conclusion","[{\"question\":\"What was the main objective of the study?\",\"answer\":\"To identify signatures of gut microbiota, fungi, and metabolites associated with severe irAEs in advanced hepatobiliary cancers, compared with mild or no irAEs.\"},{\"question\":\"How were patients grouped in the analysis?\",\"answer\":\"Patients with advanced hepatobiliary cancers were enrolled and categorized as having severe irAEs, mild irAEs, or no irAEs, with train and test sets used for model development and evaluation.\"},{\"question\":\"What predictors did the study propose for severe irAEs?\",\"answer\":\"A predictive model based on four bacterial and six metabolite features simultaneously discriminated severe irAEs from mild and no irAEs, suggesting gut microbiota- and/or metabolite-based algorithms for prediction and prognostic markers.\"}]","Gut microbiota and metabolite signatures predict severe immune-related adverse events in advanced hepatobiliary cancers | PDF",1790193497,33]