{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T04:51:24Z","timestamp":1771649484790,"version":"3.50.1"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The current understanding of colorectal carcinogenesis is based on the adenoma-carcinoma sequence, where genetics, intestinal microbiota changes and local immunity shifts seem to play the key roles. Despite the emerging evidence of dysbiotic intestinal state and immune-cell infiltration changes in patients with colorectal adenocarcinoma, early and advanced adenoma as precursors of colorectal cancer, and carcinoma <jats:italic>in situ<\/jats:italic> as the following progression, are rather less studied. The newly colon-site adapted AI-based analysis of immune infiltrates is able to predict long-term outcomes of colon carcinoma. Though it could also facilitate the pathologic evaluation of precancerous lesion\u2019s potential to progress. Therefore, the purpose of this prospective cohort study (MIMICA-1) is, firstly, to identify the intestinal microbiota and immune infiltration patterns around the normal bowel tissue, early and advanced adenoma, carcinoma in situ, and adenocarcinoma, and secondly, to analyze the immune \u2013 microbiome interplay along the steps of conventional colorectal tumorigenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and analyses<\/jats:title><jats:p>This study aims to prospectively recruit 40 patients (10 per group) with confirmed colorectal dysplasia undergoing endoscopic polypectomy, endoscopic mucosal resection for colorectal small (\u22641cm), and large (&amp;gt;1cm) adenoma or carcinoma in situ, or biopsy and subsequent colon resection for invasive colorectal cancer, and 10 healthy patients undergoing screening colonoscopy. Stool samples will be collected prior to bowel preparation for the analysis of fecal (luminal) microbiota composition. Biopsy specimens will be taken from the terminal ileum, right colon, left colon, and a pathological lesion in the colon (if present) to assess mucosa-associated microbiota composition and intestinal immunity response. DNA will be extracted from all samples and sequenced using the Illumina MiSeq platform. Unifrac and Bray-Curtis methods will be used to assess microbial diversity. The intestinal immune system response will be examined using digital image analysis where primarily immunohistochemistry procedures for CD3, CD8, CD20 and CD68 immune cell markers will be performed. Thereafter, the count, density and distribution of immunocompetent cells in epithelial and stromal tissue compartments will be evaluated using AI-based platform. The interaction between the microbial shifts and intestinal immune system response in adenoma-carcinoma sequence and the healthy patients will be examined. In addition, fecal samples will be explored for gut microbiota\u2019s composition, comparing fecal- and tissue-derived bacterial patterns in healthy gut and along the adenoma-carcinoma sequence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We hypothesize that changes within the human gut microbiota led to detectable alterations of the local immune response and correlate with the progression from normal mucosa to colorectal adenoma and invasive carcinoma. It is expectable to find more severe gut immune infiltration at dysplasia site, though analyzing invasive colorectal cancer we expect to detect broader mucosa-associated and luminal microbiota changes with subsequent local immune response at near-lesion site and possibly throughout the entire colon. We believe that specific compositional differences detected around premalignant colorectal lesions are critically important for its primary role in initiation and acceleration of colorectal carcinogenesis. Thus, these microbial patterns could potentially supplement fecal immunohistochemical tests for the early non-invasive detection of colorectal adenoma. Moreover, AI-based analysis of immune infiltrates could become additional diagnostic and prognostic tool in precancerous lesions prior to the development of colorectal cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Registration<\/jats:title><jats:p>The study is registered at the Australian New Zealand Clinical Trials Registry (ACTRN12624000976583) <jats:ext-link>https:\/\/www.anzctr.org.au\/<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2024.1495635","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T07:07:27Z","timestamp":1736147247000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Interaction of human gut microbiota and local immune system in progression of colorectal adenoma (MIMICA-1): a protocol for a prospective, observational cohort study"],"prefix":"10.3389","volume":"14","author":[{"given":"Jurate","family":"Valciukiene","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Egle","family":"Lastauskiene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aida","family":"Laurinaviciene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matas","family":"Jakubauskas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius","family":"Kryzauskas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruta Barbora","family":"Valkiuniene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renaldas","family":"Augulis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ausra","family":"Garnelyte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justinas","family":"Kavoliunas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ugne","family":"Silinskaite","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomas","family":"Poskus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"A: Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI18-1111","article-title":"Global increasing incidence of young-onset colorectal cancer across 5 continents: a joinpoint regression analysis of 1,922,167 cases","volume":"28","author":"Lui","year":"2019","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/7828392","article-title":"Study of the relationship between microbiome and colorectal cancer susceptibility using 16SrRNA sequencing","volume":"2020","author":"Liu","year":"2020","journal-title":"Hindawi BioMed Res Intern"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.1054808","article-title":"Gut microbiota signatures in tissues of the colorectal polyp and normal colorectal mucosa, and faeces","volume":"12","author":"Zhong","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1186\/s13063-019-3801-x","article-title":"Fecal microbiome as determinant of the effect of diet on colorectal cancer risk: comparison of meat-based versus pesco-vegetarian diets (the MeaTIc study)","volume":"20","author":"Sofi","year":"2019","journal-title":"Trials"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.03186-19","article-title":"Fecal metabolomic signatures in colorectal adenoma patients are associated with gut microbiota and early events of colorectal cancer pathogenesis","volume":"11","author":"Kim","year":"2020","journal-title":"mBio"},{"key":"B7","doi-asserted-by":"publisher","first-page":"6528","DOI":"10.1038\/ncomms7528","article-title":"Gut microbiome development along the colorectal adenoma-carcinoma sequence","volume":"6","author":"Feng","year":"2015","journal-title":"Nat Commun"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15051602","article-title":"Tissue vs. Fecal-derived bacterial dysbiosis in precancerous colorectal lesions: A systematic review","volume":"15","author":"Valciukiene","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0000000000000050","article-title":"Gut microbiome and colorectal adenomas","volume":"20","author":"Dulal","year":"2014","journal-title":"Cancer J"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-13-0042","article-title":"Colorectal cancer: looking for answers in the microbiota","volume":"3","author":"Jobin","year":"2013","journal-title":"Cancer Discovery"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.15430\/JCP.2017.22.2.108","article-title":"Comparisons of gut microbiota among healthy control, patients with conventional adenoma, sessile serrated adenoma, and colorectal cancer","volume":"22","author":"Yoon","year":"2017","journal-title":"J Cancer Prev"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15030866","article-title":"Gut microbiota in colorectal cancer: biological role and therapeutic opportunities","volume":"15","author":"Pandey","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B13","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1146\/annurev-micro-102215-095513","article-title":"Gut microbiota, inflammation, and colorectal cancer","volume":"70","author":"Brennan","year":"2016","journal-title":"Annu Rev Microbiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0882-8","article-title":"Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer","volume":"26","author":"Roberti","year":"2020","journal-title":"Nat Med;"},{"key":"B15","volume-title":"Embryology, Bowel","author":"Wilson","year":"2023"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.963819","article-title":"Interaction between microbiota and immunity and its implication in colorectal cancer","volume":"13","author":"Xing","year":"2022","journal-title":"Front Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01830","article-title":"Aspects of gut microbiota and immune system interactions in infectious diseases, immunopathology, and cancer","volume":"9","author":"Lazar","year":"2018","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115040","article-title":"Gut microbiota interactions with antitumor immunity in colorectal cancer: From understanding to application","volume":"165","author":"Zhuang","year":"2023","journal-title":"BioMed Pharmacother"},{"key":"B19","doi-asserted-by":"publisher","first-page":"12","DOI":"10.21767\/2471-9943.100042","article-title":"Interplay between gut microbiota and T lymphocytes in colorectal cancer","volume":"3","author":"Helal","year":"2017","journal-title":"Colorec Cancer"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1309.e1322","DOI":"10.1016\/j.ajpath.2020.01.018","article-title":"Immunogradient indicators for antitumor response assessment by automated tumor-stroma interface zone detection","volume":"190","author":"Rasmusson","year":"2020","journal-title":"Am J Pathol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12102902","article-title":"Immuno-interface score to predict outcome in colorectal cancer independent of microsatellite instability status","volume":"12","author":"Nestarenkaite","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B22","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41746-020-0275-x","article-title":"Spatial immune profiling of the colorectal tumor microenvironment predicts good outcome in stage II patients","volume":"3","author":"Nearchou","year":"2020","journal-title":"NPJ Digit Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1030745","article-title":"Effects of gut microbiota on immune responses and immunotherapy in colorectal cancer","volume":"13","author":"Hou","year":"2022","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-307873","article-title":"Spatial variation of the colonic microbiota in patients with ulcerative colitis and control volunteers","volume":"64","author":"Lavelle","year":"","journal-title":"Gut."},{"key":"B25","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41746-021-00427-2","article-title":"Interpretable survival prediction for colorectal cancer using deep learning","volume":"4","author":"Wulczyn","year":"2021","journal-title":"NPJ Digit Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.622064","article-title":"New insights into the cancer-microbiome-immune axis: decrypting a decade of discoveries","volume":"12","author":"Jain","year":"2021","journal-title":"Front Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1912129116","article-title":"Colorectal cancer-associated microbiota contributes to oncogenic epigenetic signatures","volume":"116","author":"Sobhani","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/7354260","article-title":"Colorectal cancer: from the genetic model to posttranscriptional regulation by noncoding RNAs","volume":"2017","author":"Lizarbe","year":"2017","journal-title":"BioMed Res Int"},{"key":"B29","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1101\/gad.348226.120","article-title":"Genetic and biological hallmarks of colorectal cancer","volume":"35","author":"Li","year":"2021","journal-title":"Genes Dev"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.600886","article-title":"Resolving the paradox of colon cancer through the integration of genetics, immunology, and the microbiota","volume":"11","author":"Fidelle","year":"2020","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000000871","article-title":"A guide to human microbiome research: study design, sample collection, and bioinformatics analysis","volume":"133","author":"Qian","year":"2020","journal-title":"Chin Med J (Engl)"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039743","article-title":"Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer","volume":"7","author":"Chen","year":"2012","journal-title":"PloS One"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15123065","article-title":"Distinct signatures of tumor-associated microbiota and metabolome in low-grade vs. High-grade dysplastic colon polyps: inference of their role in tumor initiation and progression","volume":"15","author":"Clavenna","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2018.08.035","article-title":"The association between fecal microbiota and different types of colorectal polyp as precursors of colorectal cancer","volume":"124","author":"Rezasoltani","year":"2018","journal-title":"Microb Pathog"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e3181577511","article-title":"Initiative S. Strengthening the reporting of observational studies in epidemiology (STROBE): explanation and elaboration","volume":"147","author":"Vandenbroucke","year":"2007","journal-title":"Ann Intern Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031446","article-title":"Tumor-associated microbiome: where do we stand","volume":"22","author":"Oliva","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1186\/1757-4749-6-26","article-title":"Co-occurrence of driver and passenger bacteria in human colorectal cancer","volume":"6","author":"Geng","year":"2014","journal-title":"Gut Pathog"},{"key":"B38","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s10916-020-1521-0","article-title":"General data protection regulation in health clinics","volume":"44","author":"Lopes","year":"2020","journal-title":"J Med Syst"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines8110489","article-title":"Gut microbiota and colorectal cancer development: A closer look to the adenoma-carcinoma sequence","volume":"8","author":"Vacante","year":"2020","journal-title":"Biomedicines"},{"key":"B40","doi-asserted-by":"publisher","first-page":"10923","DOI":"10.1038\/s41598-019-45588-z","article-title":"Enterotype-based analysis of gut microbiota along the conventional adenoma-carcinoma colorectal cancer pathway","volume":"9","author":"Yang","year":"2019","journal-title":"Sci Rep"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.5217\/ir.2018.16.3.346","article-title":"Impact of microbiota in colorectal carcinogenesis: Lessons from experimental models","volume":"16","author":"Yu","year":"2018","journal-title":"Intest. Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i48.8626","article-title":"Fusobacterium's link to colorectal neoplasia sequenced: A systematic review and future insights","volume":"23","author":"Hussan","year":"2017","journal-title":"World J Gastroenterol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-014-2081-3","article-title":"Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome","volume":"33","author":"Flanagan","year":"2014","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00566","article-title":"Global investigations of fusobacterium nucleatum in human colorectal cancer","volume":"9","author":"Lee","year":"2019","journal-title":"Front Oncol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119462","article-title":"Quantitative profiling of colorectal cancer-associated bacteria reveals associations between fusobacterium spp., enterotoxigenic Bacteroides fragilis (ETBF) and clinicopathological features of colorectal cancer","volume":"10","author":"Viljoen","year":"2015","journal-title":"PloS One"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2080-8","article-title":"Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli","volume":"580","author":"Pleguezuelos-Manzano","year":"2020","journal-title":"Nature"},{"key":"B47","doi-asserted-by":"publisher","first-page":"2925","DOI":"10.1038\/s41598-021-82465-0","article-title":"Parvimonas micra, Peptostreptococcus stomatis, Fusobacterium nucleatum and Akkermansia muciniphila as a four-bacteria biomarker panel of colorectal cancer","volume":"11","author":"Osman","year":"2021","journal-title":"Sci Rep"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12051142","article-title":"Integrative analysis of fecal metagenomics and metabolomics in colorectal cancer","volume":"12","author":"Clos-Garcia","year":"2020","journal-title":"Cancers"},{"key":"B49","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s40168-020-00875-0","article-title":"Microbiome definition re-visited: old concepts and new challenges","volume":"8","author":"Berg","year":"2020","journal-title":"Microbiome"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.841552","article-title":"Alterations in the gut microbiota and their metabolites in colorectal cancer: recent progress and future prospects","volume":"12","author":"Li","year":"2022","journal-title":"Front Oncol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2022.2038863","article-title":"The potential of fecal microbiota and amino acids to detect and monitor patients with adenoma","volume":"14","author":"Bosch","year":"2022","journal-title":"Gut Microbes"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17010","article-title":"Faecal microbial biomarkers in early diagnosis of colorectal cancer","volume":"25","author":"Olovo","year":"2021","journal-title":"J Cell Mol Med"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-1599","article-title":"Fecal bacteria act as novel biomarkers for noninvasive diagnosis of colorectal cancer","volume":"23","author":"Liang","year":"2017","journal-title":"Clin Cancer Res"},{"key":"B54","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1186\/s12885-019-5571-y","article-title":"The presence of bacteria varies between colorectal adenocarcinomas, precursor lesions and non-malignant tissue","volume":"19","author":"Bundgaard-Nielsen","year":"2019","journal-title":"BMC Cancer"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00138-20","article-title":"Meta-analysis of 16S rRNA microbial data identified distinctive and predictive microbiota dysbiosis in colorectal carcinoma adjacent tissue","volume":"5","author":"Mo","year":"2020","journal-title":"mSystems"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-309595","article-title":"Tumour-associated and non-tumour-associated microbiota in colorectal cancer","volume":"66","author":"Flemer","year":"2017","journal-title":"Gut"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9051108","article-title":"Differences in the on- and off-tumor microbiota between right- and left-sided colorectal cancer","volume":"9","author":"Phipps","year":"2021","journal-title":"Microorganisms"},{"key":"B58","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41522-022-00328-6","article-title":"Distinct colon mucosa microbiomes associated with tubular adenomas and serrated polyps","volume":"8","author":"Avelar-Barragan","year":"2022","journal-title":"NPJ Biofilms Microbiomes"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000389","article-title":"Leveraging fecal microbial markers to improve the diagnostic accuracy of the fecal immunochemical test for advanced colorectal adenoma","volume":"12","author":"Zhang","year":"2021","journal-title":"Clin Transl Gastroenterol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3390\/genes11111374","article-title":"Classification of changes in the fecal microbiota associated with colonic adenomatous polyps using a long-read sequencing platform","volume":"11","author":"Wei","year":"2020","journal-title":"Genes"},{"key":"B61","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1186\/s12967-022-03666-3","article-title":"Artificial intelligence for quantifying immune infiltrates interacting with stroma in colorectal cancer","volume":"20","author":"Yang","year":"2022","journal-title":"J Transl Med"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2023.2215541","article-title":"Artificial intelligence-assisted analysis for tumor-immune interaction within the invasive margin of colorectal cancer","volume":"55","author":"Ye","year":"2023","journal-title":"Ann Med"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-022-00548-1","article-title":"The rise to power of the microbiome: power and sample size calculation for microbiome studies","volume":"15","author":"Ferdous","year":"2022","journal-title":"Mucosal Immunol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11133613","article-title":"Gut microbiome modification through dietary intervention in patients with colorectal cancer: protocol for a prospective, interventional, controlled, randomized clinical trial in patients with scheduled surgical intervention for CRC","volume":"11","author":"Mart\u00ednez-S\u00e1nchez","year":"2022","journal-title":"J Clin Med"},{"key":"B65","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1093\/nutrit\/nuab006","article-title":"Probiotics supplementation in patients with colorectal cancer: a systematic review of randomized controlled trials","volume":"80","author":"Dikeocha","year":"2022","journal-title":"Nutr Rev"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1159\/000525695","article-title":"Intestinal microbiota: novel personalized cancer immunotherapy in colorectal cancer","volume":"183","author":"Azimi","year":"2022","journal-title":"Int Arch Allergy Immunol"},{"key":"B67","article-title":"Regulation (EU) 2016\/679 of the European parliament and of the council of 27 April 2016","volume":"119","year":"2016","journal-title":"Off J Eur Union"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2024.1495635\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T07:07:30Z","timestamp":1736147250000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2024.1495635\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,6]]},"references-count":67,"alternative-id":["10.3389\/fonc.2024.1495635"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2024.1495635","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,6]]},"article-number":"1495635"}}