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This study quantified CRC-associated Fusobacterium nucleatum and the commensal Escherichia coli in 99 colorectal cancer cases using archival tumor and adjacent normal tissues. SLC22A4/OCTN1 genotyping was performed, and CRC stem cells engineered to express the 503F variant were tested in vitro. Mutant alleles correlated with a higher F. nucleatum/E. coli ratio and reduced bacterial clearance, linking SLC22A4 function to a pro-carcinogenic intratumor microbiota.",{"@graph":69,"@context":121},[70,84,104],{"@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/genetic-variants-of-the-transporter-slc22a4-affect-the-abundance-and-survival-of-fusobacterium-nucleatum-in-colorectal-cancer/345549/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/genetic-variants-of-the-transporter-slc22a4-affect-the-abundance-and-survival-of-fusobacterium-nucleatum-in-colorectal-cancer/345549.png","ImageObject",300,407,{"name":92,"@type":93},"Miles","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-22",true,{"@type":101,"interactionType":102,"userInteractionCount":8},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"What role do intestinal microbiota and host genetics play in colorectal cancer development?","Question",{"text":111,"@type":112},"The microbiota influences CRC development, but interactions between microbial profiles and host genetic factors during tumorigenesis are not well understood. This work investigates how genetic variants of SLC22A4 shape intratumor microbes.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"How was Fusobacterium nucleatum abundance assessed in the study?",{"text":116,"@type":112},"F. nucleatum and Escherichia coli were quantified in 99 cases using archival colorectal cancer tissue and adjacent normal mucosa. Tissues were also genotyped for the SLC22A4 503F variant.",{"name":118,"@type":109,"acceptedAnswer":119},"What did the SLC22A4 503F variant change in cancer models?",{"text":120,"@type":112},"Colon cancer spheroids engineered to express the 503F variant showed an attenuated inflammatory response to F. nucleatum and impaired bacterial clearance. This mechanistically links SLC22A4 function to increased intratumor F. nucleatum abundance.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},345549,1790104442,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"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},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","GUT MICROBES  \n2026, VOL. 18, NO. 1, 2681818  \n[https://doi.org/10.1080/19490976.2026.2681818](https://doi.org/10.1080/19490976.2026.2681818)  \nRESEARCH ARTICLE     \nGenetic variants of the transporter SLC22A4 affect the abundance and survival of Fusobacterium nucleatum in colorectal cancer  \nSamah Chouaibia, b, Veronica Fertittaa, 1, Silvia Porrecaa, 1, Leila Njimc, Antonella Carcagnìd, Gabriele Toiettae, Gianluca Canettierif, Khadija Zouarig, Maha Mastourib, Yosr Kadrib and Giovambattista Pania, h   \naDepartment of Translational Medicine and Surgery, Faculty of Medicine, Università Cattolica del Sacro Cuore, Rome, bLaboratory of Transmissible Diseases and Biologically Active Substances LR99ES27, Faculty of Pharmacy, University of  \nItaly; Monastir,  \nMonastir, Tunisia; cDepartment of Pathological Anatomy and Cytology, Fattouma Bourguiba University Hospital, Monastir, Tunisia; dFacility of Epidemiology and Biostatistics–Gemelli Generator, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; eTumor Immunology and Immunotherapy Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy; fDepartment of Molecular Medicine, Sapienza University of Rome, Rome, Italy; gColorectal Diseases Research Unit, Faculty of Medicine, University of Monastir, Monastir, Tunisia; hFondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy  \nABSTRACT  \nThe intestinal microbiota influences colorectal cancer (CRC) development, but its interactions with the host's genetic profile during tumorigenesis are poorly understood. We quantified the CRC-associated pathobiont Fusobacterium nucleatum (F. nucleatum) and the commensal Escherichia coli (E. coli) in 99 cases of archival colorectal cancer and adjacent normal mucosa. Tissues were genotyped for the 503F variant of the Organic Cation Transporter OCTN1/SLC22A4 . Colorectal cancer stem cells engineered to express the variant were infected with F. nucleatum in vitro.  \nF. nucleatum was similarly present in colorectal cancer tissues and the adjacent normal mucosa, but the F. nucleatum/E. coli ratio was significantly higher in tumors (303.82 vs 30.86, p-value = 0.0396), in a fashion that steadily increased with the number of mutant SLC22A4 alleles (23 .48, 159. 56, and 211.03 for 0, 1, or 2 T alleles; p = 0.0215) . Colon cancer spheroids overexpressing the 503F variant, but not the wild-type allele, displayed attenuated inflammatory response to F. nucleatum and impaired bacterial clearance, mechanistically linking SLC22A4 function and intratumoral F. nucleatum abundance. Thus, genetic variants of the intestinal carrier SLC22A4 shape the intratumor microbiota in favor of a pro-carcinogenic pathobiont by dampening innate immunity and increasing the tolerance of cancerous cells to bacterial invasion.  \nARTICLE HISTORY  \nReceived 26 February 2026 Revised 17 April 2026 Accepted 26 May 2026  \nKEYWORDS  \nColorectal cancer;  \nFusobacterium nucleatum; microbiota; OCTN1; genetic variants; cancer stem cells; innate immunity  \nCONTACT Giovambattista Pani  [giovambattista.pani@unicatt.it](giovambattista.pani@unicatt.it)  Department of Translational Medicine and Surgery, Faculty of Medicine, 1Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, Rome, 00168, Italy  \nThese two authors have contributed equally.  \n Supplemental data for this article can be accessed online at [https://doi.org/10.1080/19490976.2026.2681818](https://doi.org/10.1080/19490976.2026.2681818) .  \n© 2026 The Author(s) . Published with license by Taylor & Francis Group, LLC.  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution License ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author","cbCaia9smbgQjkJo","https://ap.wps.com/l/cbCaia9smbgQjkJo","pdf",1827803,14,"English","# Abstract\n## Introduction","[{\"question\":\"What role do intestinal microbiota and host genetics play in colorectal cancer development?\",\"answer\":\"The microbiota influences CRC development, but interactions between microbial profiles and host genetic factors during tumorigenesis are not well understood. This work investigates how genetic variants of SLC22A4 shape intratumor microbes.\"},{\"question\":\"How was Fusobacterium nucleatum abundance assessed in the study?\",\"answer\":\"F. nucleatum and Escherichia coli were quantified in 99 cases using archival colorectal cancer tissue and adjacent normal mucosa. Tissues were also genotyped for the SLC22A4 503F variant.\"},{\"question\":\"What did the SLC22A4 503F variant change in cancer models?\",\"answer\":\"Colon cancer spheroids engineered to express the 503F variant showed an attenuated inflammatory response to F. nucleatum and impaired bacterial clearance. This mechanistically links SLC22A4 function to increased intratumor F. nucleatum abundance.\"}]","Genetic variants of the transporter SLC22A4 affect the abundance and survival of Fusobacterium nucleatum in colorectal cancer | PDF",1790058057,35]