{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T08:49:21Z","timestamp":1775983761702,"version":"3.50.1"},"posted":{"date-parts":[[2025,3,28]]},"group-title":"Immunology","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,28]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Colorectal cancer (CRC) results from the accumulation of mutations and epigenetic changes in gut epithelial cells likely due to gut microbiota dysbiosis. However, limited research has been done to explore the link between host tumour dysbiosis and disease outcome.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The mechanisms influencing outcomes of 97 colorectal cancer (CRC) patients, including 13 with Lynch syndrome, 20 with inflammatory bowel disease (IBD), and 64 sporadic cases, were analyzed using a multiomics approach. These patients were categorized into two groups: \u201cdisease-free\/stable disease\u201d and \u201cprogression disease\u201d survival outcomes. The analysis included tumor adherent microbiota composition (16S rRNA), somatic gene mutations (WES), gene expression (RNAseq), immune markers (RNAscope), and immune infiltrate cells (immunohistochemistry).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    IBD-CRC patients had worse outcomes than those with Lynch or sporadic CRC, regardless of TNM staging or treatment. Symbiotic bacteria like\n                    <jats:italic>Lactococcus lactis<\/jats:italic>\n                    were significantly reduced in IBD-CRC tissues. Patient outcomes were influenced by the abundance of virulent (\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    ) relative to beneficial bacteria (\n                    <jats:italic>Lactococcus lactis<\/jats:italic>\n                    ). Although no significant increase in deleterious somatic mutations was found in IBD-CRC. 16sRNA revealed increased virulent- and decreased anti-inflammatory symbiotic-bacteria correlating with the upregulation of oncogenes and downregulation of anti-oncogenes like PHLPP1. The multiplex\n                    <jats:italic>in situ<\/jats:italic>\n                    hybridization of CD8, IFN\u03b3 and PHLPP1 an anti-oncogene revealed significant decrease of immune cells with detectable PHLPP1 expression in IBD-CRC tumour tissues as compared to sporadic CRCs.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The poor outcomes in IBD-CRC patients are likely due to gut dysbiosis and immune cell alterations, possibly triggered by microbiota-related epigenetic pathways.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>What You Need to Know<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND AND CONTEXT<\/jats:title>\n                    <jats:p>Colorectal cancer (CRC) is associated with gut microbiota dysbiosis. Inflammatory bowel disease-related CRC (IBD-CRC) is classified as an environment-related condition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>NEW FINDINGS<\/jats:title>\n                    <jats:p>In relation with patient outcomes, tumour tissues from three types of CRC (Sporadic-, IBD-, and Lynch syndrome-CRC) were analyzed using a multiomic approach. This included examining tissue adherent virulent bacteria, gene analyses, and quantifying immune cell infiltration in the mucosa. IBD-CRC patients had the worst outcomes, associated with the down regulation of PHLPP1 gene, virulent\/symbiotic imbalance, and immune response failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS<\/jats:title>\n                    <jats:p>Lack of animal experiments using FMT of fresh stool from IBD-CRC patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CLINICAL AND TRANSLATIONAL RESEARCH RELEVANCE<\/jats:title>\n                    <jats:p>Among the different types of CRC, IBD-CRC patients showed a greater imbalance between harmful and beneficial bacteria, along with immune response failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Lay summary<\/jats:title>\n                    <jats:p>This study compares the pathological and clinical characteristics of patients with colorectal cancer (CRC) across three distinct etiologies: sporadic CRC, inflammatory bowel disease (IBD)-associated CRC, and Lynch syndrome-associated CRC (LS-CRC). Distinct differences in tumor-adherent microbiota, gene expression and immune response profiles were observed. Notably, IBD-CRC patients demonstrated the poorest prognosis depending on microbe-host gene interaction highlighting potential biomarkers for disease prognosis and treatment strategies.<\/jats:p>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.1101\/2025.03.25.645177","type":"posted-content","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T04:08:20Z","timestamp":1743221300000},"source":"Crossref","is-referenced-by-count":1,"title":["Poor prognosis in IBD-complicated colon cancer through gut dysbiosis-related immune response failure"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5113-0660","authenticated-orcid":false,"given":"Iradj","family":"Sobhani","sequence":"first","affiliation":[{"name":"Service de Gastroenterologie, APHP, Hopital Henri Mondor, F-94010 Cr\u00e9teil-France"},{"name":"EA7375 \u2013 EC2M3 Universit\u00e9 Paris Est Cr\u00e9teil (UPEC); F-94000 Cr\u00e9teil France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0400-882X","authenticated-orcid":false,"given":"Nilmara","family":"De Oliveira Alves","sequence":"additional","affiliation":[{"name":"ONCOLille, Universite de Lille, Inserm, U1003, Lille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Sadeghi","sequence":"additional","affiliation":[{"name":"EA7375 \u2013 EC2M3 Universit\u00e9 Paris Est Cr\u00e9teil (UPEC); F-94000 Cr\u00e9teil France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecile","family":"Charpy","sequence":"additional","affiliation":[{"name":"EA7375 \u2013 EC2M3 Universit\u00e9 Paris Est Cr\u00e9teil (UPEC); F-94000 Cr\u00e9teil France"},{"name":"ONCOLille, Universite de Lille, Inserm, U1003, Lille, France"},{"name":"Service d\u2019Anatomie pathologique, APHP, Hopital Henri Mondor, F-Cr\u00e9teil-94010 France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9486-3103","authenticated-orcid":false,"given":"Emma","family":"Bergsten","sequence":"additional","affiliation":[{"name":"EA7375 \u2013 EC2M3 Universit\u00e9 Paris Est Cr\u00e9teil (UPEC); F-94000 Cr\u00e9teil France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aur\u00e9lien","family":"Amiot","sequence":"additional","affiliation":[{"name":"Service de Gastroenterologie, APHP, Hopital Henri Mondor, F-94010 Cr\u00e9teil-France"},{"name":"EA7375 \u2013 EC2M3 Universit\u00e9 Paris Est Cr\u00e9teil (UPEC); F-94000 Cr\u00e9teil France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Barau","sequence":"additional","affiliation":[{"name":"Plateforme de Ressources Biologiques, APHP, Hopital Henri Mondor, F-94010 Cr\u00e9teil-France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Brunetti","sequence":"additional","affiliation":[{"name":"Service de Chirurgie digestive, APHP, Hopital Henri Mondor, F-94010 Cr\u00e9teil-France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2397-4230","authenticated-orcid":false,"given":"Amaury","family":"Vaysse","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Bioinformatics and Biostatistics Hub, Paris-France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Tournigand","sequence":"additional","affiliation":[{"name":"Service d\u2019oncologie m\u00e9dicale, AP-HP, Hopital Henri Mondor, F-94010 Creteil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0243-9717","authenticated-orcid":false,"given":"Mathias","family":"Chamaillard","sequence":"additional","affiliation":[{"name":"ONCOLille, Universite de Lille, Inserm, U1003, Lille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khashayarsha","family":"Khazaie","sequence":"additional","affiliation":[{"name":"Department of Immunology & Cancer Biology, Mayo Clinic, AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Mestivier","sequence":"additional","affiliation":[{"name":"EA7375 \u2013 EC2M3 Universit\u00e9 Paris Est Cr\u00e9teil (UPEC); F-94000 Cr\u00e9teil France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041201221245000_2025.03.25.645177v1.1","unstructured":"Anon. 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