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Using Mendelian randomization and Bayesian colocalization on GWAS data, the study identifies gut genera causally associated with breast cancer risk and combines multi-omics profiling in HFD-fed breast cancer mouse models with in vitro co-culture and in vivo experiments focused on Roseburia intestinalis and Streptococcus mutans.",{"@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/high-fat-diet-reshapes-microbial-interactions-to-promote-breast-cancer-stemness-via-streptococcus-mutans-induced-leucine-accumulation/360817/",{"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/high-fat-diet-reshapes-microbial-interactions-to-promote-breast-cancer-stemness-via-streptococcus-mutans-induced-leucine-accumulation/360817.png","ImageObject",300,407,{"name":92,"@type":93},"Bulrr","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What question does the study address about high-fat diet and breast cancer?","Question",{"text":112,"@type":113},"The study investigates how HFD-induced changes in gut microbiota interactions can influence breast cancer progression through microbial metabolites and cancer stemness.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which gut microbes are highlighted as important in the findings?",{"text":117,"@type":113},"Roseburia intestinalis is identified as a potential causal risk factor, and HFD promotes co-occurrence with Streptococcus mutans, supporting intratumoral colonization and downstream effects.",{"name":119,"@type":110,"acceptedAnswer":120},"How does Streptococcus mutans affect breast cancer stemness in this work?",{"text":121,"@type":113},"Streptococcus mutans-derived leucine accumulates in the tumor microenvironment and robustly enhances breast cancer cell proliferation and stemness, including increased tumor sphere formation and stemness marker expression.","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},360817,1790193630,{"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":81,"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},5909892115043,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Cheng et al. Breast Cancer Research (2026) 28:124 Breast Cancer Research  \n[https://doi.org/10.1186/s13058-026-02297-6](https://doi.org/10.1186/s13058-026-02297-6)  \nRESEARCH Open Access  \nHigh-fat diet reshapes microbial interactions to promote breast cancer stemness via Streptococcus mutans-induced leucine accumulation  \nChao Cheng1,2†, Fahu Yuan3†, Jincheng Li4,5, Yixian Fan5, Yang Liu1, Quan Zhang6, Yanjun Lu7 and Lei He8*  \nAbstract  \nBackground Obesity and high-fat diet (HFD) are established risk factors for breast cancer, but the mechanisms by which dietary-induced gut microbiota alterations influence cancer progression are not fully understood. The interplay between microbial composition, metabolites, and cancer progression warrants further exploration.  \nMethods We employed Mendelian randomization (MR) and Bayesian colocalization analyses based on genomewide association studies (GWAS) to identify gut microbial genera causally linked to breast cancer risk. Multi-omics, including 16S rRNA sequencing, fecal metabolomics and RNA-seq, were performed to depict HFD-induced microbial and metabolic shifts in breast cancer-bearing mice. In vitro co-culture systems and in vivo murine models examined interactions between Roseburia intestinalis (R. intestinalis) and Streptococcus mutans (S. mutans) under HFD conditions. Functional assays, including immunofluorescence, qRT-PCR, probe-based assays and fluorescent in situ hybridization, and flow cytometry, evaluated cancer stemness, bacterial colonization, and the impact of leucine metabolism.  \nResults MR analysis revealed Roseburia as a potential causal microbial risk factor for breast cancer, with colocalized genes enriched in fatty acid metabolism. HFD feeding promoted the co-occurrence of R. intestinalis and S. mutans, facilitating S. mutans intratumoral colonization and consequent leucine accumulation in the tumor microenvironment (TME) . S. mutans-derived leucine robustly enhanced breast cancer cell proliferation and stemness, as evidenced by increased tumor sphere formation and upregulation of CD44, CD133, and SOX2 . Functional blockade of leucine transport with BCH attenuated S. mutans-mediated tumor growth and limited tumor-associated macrophage activation in vivo.  \nConclusions This study reveals that HFD-induced reshaping of microbial interactions, particularly a commensallike interaction between S. mutans and R. intestinalis, is associated with leucine accumulation in theTME, thereby supporting breast cancer stemness and progression. Targeting S. mutans-mediated leucine accumulation represents a  \n†Chao Cheng and Fahu Yuan have contributed equally to this work.  \n*Correspondence: Lei He [leihe@hust.edu.cn](leihe@hust.edu.cn)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/licenses/by-nc-nd/4.0/](vecommons.org/licenses/by-nc-nd/4.0/.)[.](vecommons.org/licenses/by-nc-nd/4.0/.)  \nCheng et al. Breast Cancer Research (2026) 28:124","cbCaipzbGA7FWEtR","https://ap.wps.com/l/cbCaipzbGA7FWEtR","pdf",17254839,"English","# Abstract\n# Background\n# Methods\n# Results\n# Conclusions\n## Keywords","[{\"question\":\"What question does the study address about high-fat diet and breast cancer?\",\"answer\":\"The study investigates how HFD-induced changes in gut microbiota interactions can influence breast cancer progression through microbial metabolites and cancer stemness.\"},{\"question\":\"Which gut microbes are highlighted as important in the findings?\",\"answer\":\"Roseburia intestinalis is identified as a potential causal risk factor, and HFD promotes co-occurrence with Streptococcus mutans, supporting intratumoral colonization and downstream effects.\"},{\"question\":\"How does Streptococcus mutans affect breast cancer stemness in this work?\",\"answer\":\"Streptococcus mutans-derived leucine accumulates in the tumor microenvironment and robustly enhances breast cancer cell proliferation and stemness, including increased tumor sphere formation and stemness marker expression.\"}]","High-fat diet reshapes microbial interactions to promote breast cancer stemness via Streptococcus mutans-induced leucine accumulation | PDF",1790141687,48]