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      <journal-id journal-id-type="publisher-id">odmj</journal-id>
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        <journal-title xml:lang="en">OncoDaily Medical Journal</journal-title>
        <abbrev-journal-title abbrev-type="publisher">ODMJ</abbrev-journal-title>
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      <issn pub-type="epub">3067-6444</issn>
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        <publisher-name>OncoDaily Medical Journal</publisher-name>
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          <country>US</country>
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      <article-id pub-id-type="publisher-id">7451</article-id>
      <article-id pub-id-type="doi">10.69690/ODMJ-001-0426-7451</article-id>
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          <subject>Original Research</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Distinct differences in the tumour-resident microbiome between early- and late-onset colorectal cancer</article-title>
      </title-group>
      <contrib-group content-type="author">
        <contrib contrib-type="author">
          <name name-style="western">
            <surname>Waddell</surname>
            <given-names>Oliver</given-names>
          </name>
          <aff xml:lang="en">Department of Surgery and Critical Care, University of Otago, Christchurch, New Zealand</aff>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="western">
            <surname>Sulit</surname>
            <given-names>Arielle</given-names>
          </name>
          <aff xml:lang="en">Department of Surgery and Critical Care, University of Otago, Christchurch, New Zealand</aff>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="western">
            <surname>Wilson</surname>
            <given-names>Kasmira</given-names>
          </name>
          <aff xml:lang="en">Sir Peter MacCallum Department of Oncology, The University of Melbourne, Australia</aff>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="western">
            <surname>Ramsey</surname>
            <given-names>Rob</given-names>
          </name>
          <aff xml:lang="en">Sir Peter MacCallum Department of Oncology, The University of Melbourne, Australia</aff>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="western">
            <surname>Heriot</surname>
            <given-names>Alexander</given-names>
          </name>
          <aff xml:lang="en">Sir Peter MacCallum Department of Oncology, The University of Melbourne, Australia</aff>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="western">
            <surname>Frizelle</surname>
            <given-names>Frank</given-names>
          </name>
          <aff xml:lang="en">Department of Surgery and Critical Care, University of Otago, Christchurch, New Zealand</aff>
        </contrib>
        <contrib contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Purcell</surname>
            <given-names>Rachel</given-names>
          </name>
          <aff xml:lang="en">Department of Surgery and Critical Care, University of Otago, Christchurch, New Zealand</aff>
          <email>rachel.purcell@otago.ac.nz</email>
        </contrib>
      </contrib-group>
      <pub-date date-type="pub" publication-format="electronic">
        <day>26</day>
        <month>04</month>
        <year>2026</year>
      </pub-date>
      <elocation-id>ODMJ-001-0426-7451</elocation-id>
      <permissions>
        <copyright-statement>Copyright (c) 2026 OncoDaily Medical Journal</copyright-statement>
        <copyright-year>2026</copyright-year>
        <copyright-holder>OncoDaily Medical Journal</copyright-holder>
      </permissions>
      <self-uri xlink:href="https://oncodailyjournal.com/10.69690/odmj-001-0426-7451/"/>
      <kwd-group xml:lang="en">
        <kwd>Cancer Care</kwd>
        <kwd>colorectal cancer</kwd>
        <kwd>GI oncology</kwd>
        <kwd>OncoDaily Medical Journal</kwd>
        <kwd>Oncology</kwd>
        <kwd>Original Research</kwd>
        <kwd>Tumor-resident microbiome</kwd>
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  </front>
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  <back>
    <ref-list>
      <ref id="R1">
        <mixed-citation>Siegel RL, Soerjomataram I, Hayes RB, Bray F, Weber TK, Jemal A. Global patterns and trends in colorectal cancer incidence in young adults. Gut. 2019;68:2179-2185.</mixed-citation>
      </ref>
      <ref id="R2">
        <mixed-citation>Waddell O, Pearson J, McCombie A, et al. The incidence of early onset colorectal cancer in Aotearoa New Zealand: 2000-2020. BMC Cancer. 2024;24(1):456.</mixed-citation>
      </ref>
      <ref id="R3">
        <mixed-citation>Gandhi J, Davidson C, Hall C, et al. Population-based study demonstrating an increase in colorectal cancer in young patients. British Journal of Surgery. 2017;104(8):1063-1068.</mixed-citation>
      </ref>
      <ref id="R4">
        <mixed-citation>Bailey CE, Hu CY, You YN, et al. Increasing disparities in age-related incidence of colon and rectal cancer in the United States, 1975-2010. JAMA Surg. 2015;150(1)</mixed-citation>
      </ref>
      <ref id="R5">
        <mixed-citation>Abdelsattar ZM, Wong SL, Regenbogen SE, Jomaa DM, Hardiman KM, Hendren S. Colorectal cancer outcomes and treatment patterns in patients too young for average-risk screening. Cancer. 2016;122(6):929-934.</mixed-citation>
      </ref>
      <ref id="R6">
        <mixed-citation>O’connell JB, Maggard MA, Liu JH, Etzioni DA, Livingston EH, Ko CY. Do Young Colon Cancer Patients Have Worse Outcomes? 2004.</mixed-citation>
      </ref>
      <ref id="R7">
        <mixed-citation>Kolarich A, Thomas ;, George J, et al. Rectal Cancer Patients Younger Than 50 Years Lack a Survival Benefit From NCCN Guideline-Directed Treatment for Stage II and III Disease. Cancer. 2018;124:3510-3519.</mixed-citation>
      </ref>
      <ref id="R8">
        <mixed-citation>Chittleborough TJ, Gutlic I, Pearson JF, et al. Increasing incidence of young-onset colorectal carcinoma A 3-country population analysis. Dis Colon Rectum. 2020;63(7):903-910.</mixed-citation>
      </ref>
      <ref id="R9">
        <mixed-citation>Wild CP. Complementing the genome with an “exposome”: the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomarkers Prev. 2005;14(8):1847-1850.</mixed-citation>
      </ref>
      <ref id="R10">
        <mixed-citation>Hofseth LJ, Hebert JR, Chanda A, et al. Early-onset colorectal cancer: initial clues and current views. Nat Rev Gastroenterol Hepatol. 2020;17(6):352-364.</mixed-citation>
      </ref>
      <ref id="R11">
        <mixed-citation>Moon JY, Kye BH, Ko SH, Yoo RN. Sulfur Metabolism of the Gut Microbiome and Colorectal Cancer: The Threat to the Younger Generation. Nutrients 2023, Vol 15, Page 1966. 2023;15(8):1966.</mixed-citation>
      </ref>
      <ref id="R12">
        <mixed-citation>Keenan JI, Frizelle FA. Toxigenic gut bacteria, diet and colon carcinogenesis. J R Soc N Z. 2020;50(3):418-433.</mixed-citation>
      </ref>
      <ref id="R13">
        <mixed-citation>Louis P, Hold GL, Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol. 2014;12(10):661-672.</mixed-citation>
      </ref>
      <ref id="R14">
        <mixed-citation>Purcell R V, Pearson J, Aitchison A, Dixon L, Frizelle FA, Keenan JI. Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia. PLoS One. 2017;12(2).</mixed-citation>
      </ref>
      <ref id="R15">
        <mixed-citation>Zhong L, Zhang X, Covasa M. Emerging roles of lactic acid bacteria in protection against colorectal cancer. World Journal of Gastroenterology : WJG. 2014;20(24):7878.</mixed-citation>
      </ref>
      <ref id="R16">
        <mixed-citation>Faghfoori Z, Faghfoori MH, Saber A, Izadi A, Yari Khosroushahi A. Anticancer effects of bifidobacteria on colon cancer cell lines. Cancer Cell Int. 2021;21(1):1-12.</mixed-citation>
      </ref>
      <ref id="R17">
        <mixed-citation>Kong C, Liang L, Liu G, et al. Integrated metagenomic and metabolomic analysis reveals distinct gut-microbiome-derived phenotypes in early-onset colorectal cancer. Gut. 2023;72(6):1129-1142.</mixed-citation>
      </ref>
      <ref id="R18">
        <mixed-citation>Barot S V., Sangwan N, Nair KG, et al. Distinct intratumoral microbiome of young-onset and average-onset colorectal cancer. EBioMedicine. 2024;100.</mixed-citation>
      </ref>
      <ref id="R19">
        <mixed-citation>Purcell R V., Schmeier S, Lau YC, Pearson JF, Frizelle FA. Molecular subtyping improves prognostication of Stage 2 colorectal cancer. BMC Cancer. 2019;19(1):1-9.</mixed-citation>
      </ref>
      <ref id="R20">
        <mixed-citation>Sulit AK, Wilson K, Pearson J, et al. Human gene and microbial analyses in rectal cancer complete responses to radiotherapy. BJS Open. 2023;7(3).</mixed-citation>
      </ref>
      <ref id="R21">
        <mixed-citation>Purcell R V., Visnovska M, Biggs PJ, Schmeier S, Frizelle FA. Distinct gut microbiome patterns associate with consensus molecular subtypes of colorectal cancer. Scientific Reports 2017 7:1. 2017;7(1):1-12.</mixed-citation>
      </ref>
      <ref id="R22">
        <mixed-citation>Sulit AK, Daigneault M, Allen-Vercoe E, et al. Bacterial lipopolysaccharide modulates immune response in the colorectal tumor microenvironment. npj Biofilms and Microbiomes 2023 9:1. 2023;9(1):1-8.</mixed-citation>
      </ref>
      <ref id="R23">
        <mixed-citation>Sulit AK, Wilson K, Pearson J, et al. Human gene and microbial analyses in rectal cancer complete responses to radiotherapy. BJS Open. 2023;7(3).</mixed-citation>
      </ref>
      <ref id="R24">
        <mixed-citation>Sulit AK, Kolisnik T, Frizelle FA, Purcell R, Schmeier S. MetaFunc: taxonomic and functional analyses of high throughput sequencing for microbiomes. Gut Microbiome. 2023;4:e4.</mixed-citation>
      </ref>
      <ref id="R25">
        <mixed-citation>Menzel P, Ng KL, Krogh A. Fast and sensitive taxonomic classification for metagenomics with Kaiju. Nat Commun. 2016;7.</mixed-citation>
      </ref>
      <ref id="R26">
        <mixed-citation>McMurdie PJ, Holmes S. phyloseq: An R Package for Reproducible Interactive Analysis and Graphics of Microbiome Census Data. PLoS One. 2013;8(4):e61217.</mixed-citation>
      </ref>
      <ref id="R27">
        <mixed-citation>Love, M.I., W. Huber, and S. Anders, Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol, 2014. 15(12): p. 550.</mixed-citation>
      </ref>
      <ref id="R28">
        <mixed-citation>Risso, D., et al., A general and flexible method for signal extraction from single-cell RNA-seq data. Nat Commun, 2018. 9(1): p. 284.</mixed-citation>
      </ref>
      <ref id="R29">
        <mixed-citation>Flynn KJ, Ruffin MT, Kim Turgeon D, Schloss PD. Spatial variation of the native colon microbiota in healthy adults. Cancer Prevention Research. 2018;11(7):393-401.</mixed-citation>
      </ref>
      <ref id="R30">
        <mixed-citation>Kirzin S, Marisa L, Guimbaud R, et al. Sporadic Early-Onset Colorectal Cancer Is a Specific Sub-Type of Cancer: A Morphological, Molecular and Genetics Study. PLoS One. 2014;9(8):e103159.</mixed-citation>
      </ref>
      <ref id="R31">
        <mixed-citation>Chouhan H, Ferrandon S, Devecchio J, Kalady MF, Church JM. A Changing Spectrum of Colorectal Cancer Biology with Age: Implications for the Young Patient. Dis Colon Rectum. 2019;62(1):21-26.</mixed-citation>
      </ref>
      <ref id="R32">
        <mixed-citation>Marx O, Mankarious M, Yochum G. Molecular genetics of early-onset colorectal cancer. World J Biol Chem. 2023;14(2):13.</mixed-citation>
      </ref>
      <ref id="R33">
        <mixed-citation>Xu Z, Lv Z, Chen F, et al. Dysbiosis of human tumor microbiome and aberrant residence of Actinomyces in tumor-associated fibroblasts in young-onset colorectal cancer. Front Immunol. 2022;13:1008975.</mixed-citation>
      </ref>
      <ref id="R34">
        <mixed-citation>Alam MT, Amos GCA, Murphy ARJ, Murch S, Wellington EMH, Arasaradnam RP. Microbial imbalance in inflammatory bowel disease patients at different taxonomic levels. Gut Pathog. 2020 Jan 4;12:1.</mixed-citation>
      </ref>
      <ref id="R35">
        <mixed-citation>Carroll IM, Ringel-Kulka T, Siddle JP, Ringel Y. Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterology &amp; Motility. 2012;24(6):521-e248.</mixed-citation>
      </ref>
      <ref id="R36">
        <mixed-citation>Pinart M, Dötsch A, Schlicht K, et al. Gut microbiome composition in obese and non-obese persons: A systematic review and meta-analysis. Nutrients. 2022;14(1).</mixed-citation>
      </ref>
      <ref id="R37">
        <mixed-citation>Johnson KVA. Gut microbiome composition and diversity are related to human personality traits. Hum Microb J. 2020;15:100069.</mixed-citation>
      </ref>
      <ref id="R38">
        <mixed-citation>Jakobsson HE, Abrahamsson TR, Jenmalm MC, et al. Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section. Gut. 2014;63(4):559-566.</mixed-citation>
      </ref>
      <ref id="R39">
        <mixed-citation>Mosca A, Leclerc M, Hugot JP. Gut microbiota diversity and human diseases: Should we reintroduce key predators in our ecosystem? Front Microbiol. 2016;7(MAR):178205.</mixed-citation>
      </ref>
      <ref id="R40">
        <mixed-citation>Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486(7402):222.</mixed-citation>
      </ref>
      <ref id="R41">
        <mixed-citation>Wang YC, Bleich SN, Gortmaker SL. Increasing caloric contribution from sugar-sweetened beverages and 100% fruit juices among US children and adolescents, 1988-2004. Pediatrics. 2008;121(6).</mixed-citation>
      </ref>
      <ref id="R42">
        <mixed-citation>Satokari R. High Intake of Sugar and the Balance between Pro- and Anti-Inflammatory Gut Bacteria. Nutrients 2020, Vol 12, Page 1348. 2020;12(5):1348.</mixed-citation>
      </ref>
      <ref id="R43">
        <mixed-citation>Hur J, Otegbeye E, Joh HK, et al. Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women. Gut. 2021;70(12):2330-2336.</mixed-citation>
      </ref>
      <ref id="R44">
        <mixed-citation>Sanford NN, Giovannucci EL, Ahn C, Dee EC, Mahal BA. Obesity and younger versus older onset colorectal cancer in the United States, 1998–2017. J Gastrointest Oncol. 2020;11(1):121.</mixed-citation>
      </ref>
      <ref id="R45">
        <mixed-citation>Dik VK, van Oijen MGH, Smeets HM, Siersema PD. Frequent Use of Antibiotics Is Associated with Colorectal Cancer Risk: Results of a Nested Case–Control Study. Dig Dis Sci. 2016;61(1):255-264.</mixed-citation>
      </ref>
      <ref id="R46">
        <mixed-citation>Jiang F, Boakye D, Sun J, et al. Association between antibiotic use during early life and early-onset colorectal cancer risk overall and according to polygenic risk and FUT2 genotypes. Int J Cancer. Published online 2023.</mixed-citation>
      </ref>
      <ref id="R47">
        <mixed-citation>Moon JY, Kye BH, Ko SH, Yoo RN. Sulfur Metabolism of the Gut Microbiome and Colorectal Cancer: The Threat to the Younger Generation. Nutrients 2023, Vol 15, Page 1966. 2023;15(8):1966.</mixed-citation>
      </ref>
      <ref id="R48">
        <mixed-citation>Li S, Keenan JI, Shaw IC, Frizelle FA. Could Microplastics Be a Driver for Early Onset Colorectal Cancer? Cancers 2023, Vol 15, Page 3323. 2023;15(13):3323.</mixed-citation>
      </ref>
      <ref id="R49">
        <mixed-citation>Odamaki T, Kato K, Sugahara H, et al. Age-related changes in gut microbiota composition from newborn to centenarian: A cross-sectional study. BMC Microbiol. 2016;16(1):1-12.</mixed-citation>
      </ref>
      <ref id="R50">
        <mixed-citation>Hildebrand F, Gossmann TI, Frioux C, et al. Dispersal strategies shape persistence and evolution of human gut bacteria. Cell Host Microbe. 2021;29(7):1167-1176.e9.</mixed-citation>
      </ref>
      <ref id="R51">
        <mixed-citation>Carmichael WW. Cyanobacteria secondary metabolites—the cyanotoxins. Journal of Applied Bacteriology. 1992;72(6):445-459.</mixed-citation>
      </ref>
      <ref id="R52">
        <mixed-citation>Fan H, Cai Y, Xie P, et al. Microcystin-LR stabilizes c-myc protein by inhibiting protein phosphatase 2A in HEK293 cells. Toxicology. 2014;319(1):69-74.</mixed-citation>
      </ref>
      <ref id="R53">
        <mixed-citation>Erisman MD, Rothberg PG, Diehl RE, Morse CC, Spandorfer JM, Astrin SM. Deregulation of c-myc Gene Expression in Human Colon Carcinoma Is Not Accompanied by Amplification or Rearrangement of the Gene. Mol Cell Biol. 1985;5(8):1969-1976.</mixed-citation>
      </ref>
      <ref id="R54">
        <mixed-citation>Tang Y, Yi X, Zhang X, et al. Microcystin-leucine arginine promotes colorectal cancer cell proliferation by activating the PI3K/Akt/Wnt/β-catenin pathway. Oncol Rep. 2023;49(1).</mixed-citation>
      </ref>
      <ref id="R55">
        <mixed-citation>Zhu L, Hai Y, Kun C. Relationship between microcystin in drinking water and colorectal cancer. Biomed Environ Sci. 2002;15(2).</mixed-citation>
      </ref>
      <ref id="R56">
        <mixed-citation>Wood SA, Holland PT, Stirling DJ, et al. Survey of cyanotoxins in New Zealand water bodies between 2001 and 2004. N Z J Mar Freshwater Res. 2006;40(4):585-597.</mixed-citation>
      </ref>
      <ref id="R57">
        <mixed-citation>Paerl HW, Huisman J. Climate: Blooms like it hot. Science (1979). 2008;320(5872):57-58.</mixed-citation>
      </ref>
      <ref id="R58">
        <mixed-citation>Li J, Li Y, Zhou Y, Wang C, Wu B, Wan J. Actinomyces and Alimentary Tract Diseases: A Review of Its Biological Functions and Pathology. Biomed Res Int. 2018;2018.</mixed-citation>
      </ref>
      <ref id="R59">
        <mixed-citation>Gong J, Yu J, Yin S, et al. Mesenteric Adipose Tissue-Derived Klebsiella variicola Disrupts Intestinal Barrier and Promotes Colitis by Type VI Secretion System. Advanced Science. 2023;10(12):2205272.</mixed-citation>
      </ref>
      <ref id="R60">
        <mixed-citation>World Health Organisation (WHO). Oral health. 2023.</mixed-citation>
      </ref>
      <ref id="R61">
        <mixed-citation>Kitamoto S, Nagao-Kitamoto H, Jiao Y, et al. The Intermucosal Connection between the Mouth and Gut in Commensal Pathobiont-Driven Colitis. Cell. 2020;182(2):447-462.e14.</mixed-citation>
      </ref>
      <ref id="R62">
        <mixed-citation>Li X, Zhang S, Guo G, Han J, Yu J. Gut microbiome in modulating immune checkpoint inhibitors. EBioMedicine. 2022;82.</mixed-citation>
      </ref>
      <ref id="R63">
        <mixed-citation>Lu Y, Yuan X, Wang M, et al. Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies. Journal of Hematology &amp; Oncology 2022 15:1. 2022;15(1):1-20.</mixed-citation>
      </ref>
      <ref id="R64">
        <mixed-citation>Huang J, Liu W, Kang W, et al. Effects of microbiota on anticancer drugs: Current knowledge and potential applications. EBioMedicine. 2022;83.</mixed-citation>
      </ref>
      <ref id="R65">
        <mixed-citation>Sun S, Zhu X, Huang X, et al. On the robustness of inference of association with the gut microbiota in stool, rectal swab and mucosal tissue samples. Scientific Reports |. 123AD;11:14828.</mixed-citation>
      </ref>
      <ref id="R66">
        <mixed-citation>Tjalsma H, Boleij A, Marchesi JR, Dutilh BE. A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects. Nat Rev Microbiol. 2012;10(8):575-582.</mixed-citation>
      </ref>
      <ref id="R67">
        <mixed-citation>Hajishengallis G, Darveau RP, Curtis MA. The keystone-pathogen hypothesis. Nat Rev Microbiol. 2012;10(10):717-725.</mixed-citation>
      </ref>
      <ref id="R68">
        <mixed-citation>Hatakeyama M. Helicobacter pylori CagA and gastric cancer: a paradigm for hit-and-run carcinogenesis. Cell Host Microbe. 2014;15(3):306-316.</mixed-citation>
      </ref>
    </ref-list>
  </back>
</article>
