{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:59:33Z","timestamp":1790085573109,"version":"4.0.1"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI23\/00601"],"award-info":[{"award-number":["PI23\/00601"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["REVERT (GA848098)"],"award-info":[{"award-number":["REVERT (GA848098)"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundaci\u00f3n Espa\u00f1ola de Trombosis y Hemostasia","award":["Justo Aznar postdoctoral fellowship"],"award-info":[{"award-number":["Justo Aznar postdoctoral fellowship"]}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["RYC2022-037702-I"],"award-info":[{"award-number":["RYC2022-037702-I"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["RYC2023-043193-I"],"award-info":[{"award-number":["RYC2023-043193-I"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSystems"],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Colorectal cancer (CRC) arises through distinct molecular and histological routes that may be shaped by interactions between the mucosa-associated microbiota and host epigenetic regulation. We analyzed paired tumor and adjacent non-tumor colorectal mucosa from CRC patients stratified by histological subtype (conventional vs serrated-pathway groups). Microbiota composition was profiled by Illumina sequencing, and host DNA methylation was assessed using genome-wide CpG arrays with targeted validation. Alpha diversity showed modest tumor\u2013non-tumor differences, with variation by anatomical location driven by distal tumors. Differential abundance testing identified tumor-associated genera, and linear discriminant modeling highlighted taxa with high discriminatory power, including\n                      <jats:italic toggle=\"yes\">Bacteroides<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Eubacterium<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Fusobacterium<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Acinetobacter<\/jats:italic>\n                      . Methylome ordination separated tumor from non-tumor samples and revealed prominent contributions of zinc finger (ZNF) loci. Integrative latent-variable modeling (PLS\/sparse partial least squares and multi-block sparse partial least squares discriminant analysis) supported coordinated microbiome\u2013methylome variation distinguishing tumor from non-tumor mucosa, prioritized a limited set of bacterial and methylation signals, and suggested partial discrimination between conventional and serrated tumor profiles, particularly in the methylome block. Focusing on\n                      <jats:italic toggle=\"yes\">Fusobacterium<\/jats:italic>\n                      , methylation changes in selected host loci were associated with its abundance, and qPCR-based quantification of\n                      <jats:italic toggle=\"yes\">Fusobacterium nucleatum<\/jats:italic>\n                      correlated with CpG methylation at ZNF788.\n                      <jats:italic toggle=\"yes\">F. nucleatum<\/jats:italic>\n                      levels were also associated with serrated\/microsatellite instability-related CRC features and more advanced disease. These findings identify subtype-aware microbiome\u2013methylome signatures in CRC and highlight ZNF788 methylation as a candidate epigenetic correlate of intratumoral\n                      <jats:italic toggle=\"yes\">F. nucleatum<\/jats:italic>\n                      burden.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Colorectal cancer does not develop in a single way, and different tumor types may interact differently with bacteria living on the bowel lining. This study examined both tissue-associated bacteria and DNA methylation, an epigenetic mark that helps regulate genes, in paired tumor and nearby non-tumor tissue from patients with colorectal cancer. By analyzing these two layers together, we identified microbial and host methylation patterns linked to tumor tissue and to serrated-pathway cancers. In particular,\n                        <jats:italic toggle=\"yes\">Fusobacterium nucleatum<\/jats:italic>\n                        was associated with serrated\/microsatellite instability-related features, more advanced disease, and methylation of the host gene\n                        <jats:italic toggle=\"yes\">ZNF788<\/jats:italic>\n                        . These findings suggest that combining microbiome and epigenetic information may help explain why colorectal cancer subtypes behave differently and may support future subtype-aware biomarkers.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msystems.00622-26","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:06:48Z","timestamp":1787576808000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Integrative microbiome\u2013methylome analysis links bacterial taxa to colorectal cancer histological subtypes"],"prefix":"10.1128","volume":"11","author":[{"given":"\u00c1ngel","family":"Escudero-Jim\u00e9nez","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04a5hr295","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Parasitology, Complejo Hospitalario Universitario de Albacete","place":["Albacete, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Gal\u00e1n-Ros","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda y Parasitolog\u00eda, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca","place":["Murcia, Spain"]},{"id":[{"id":"https:\/\/ror.org\/051fvq837","id-type":"ROR","asserted-by":"publisher"}],"name":"Group of Molecular Pathology and Pharmacogenetics, Instituto Murciano de Investigaci\u00f3n Biosanitaria, Hospital General Universitario Santa Luc\u00eda","place":["Cartagena, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Huertas-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Marbyt\u2014Smart Solutions for Biotechnology S. 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