{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T14:20:02Z","timestamp":1789395602437,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research, Development, and Innovation Authority (RDIA)\u2014Kingdom of Saudi Arabia","award":["13263-Tabuk-2023-UT-R-3-1-hw"],"award-info":[{"award-number":["13263-Tabuk-2023-UT-R-3-1-hw"]}]},{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia","doi-asserted-by":"publisher","award":["PNURSP2026R924"],"award-info":[{"award-number":["PNURSP2026R924"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PNURSP2026R924"],"award-info":[{"award-number":["PNURSP2026R924"]}],"id":[{"id":"https:\/\/ror.org\/05b0cyh02","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Increasing evidence suggests that intestinal microbial dysbiosis contributes to colorectal tumorigenesis by reshaping host molecular signaling and the tumor immune microenvironment. However, the molecular mechanisms linking microbiome-associated alterations to host regulatory networks and disease progression remain incompletely understood. Objective: This study aimed to identify the microbiome-associated molecular regulators and immune modulators involved in colorectal cancer through an integrative multi-omics systems biology approach. Methods: Publicly available transcriptomic datasets were analyzed to identify differentially expressed genes, followed by functional enrichment, protein-protein interaction network construction, hub gene prioritization, immune infiltration profiling, survival analysis, and multi-omics characterization. Results: The identified hub genes represent hypothesis-generating host candidates for further mechanistic and clinical validation. These genes occupied key positions within host regulatory networks and were significantly associated with adverse clinical outcomes and altered CD8+ T-cell infiltration, suggesting their involvement in immune remodeling within the tumor microenvironment. Multi-omics characterization demonstrated that PTEN and SMAD4 alterations were predominantly associated with genomic deletions, whereas SMAD2 dysregulation was associated with transcriptomic and gene-dosage variation. Although the overall mutational burden of the identified hub genes was not significantly associated with disease-free survival (p = 0.878), these molecular regulators showed associations with immune-cell infiltration and CRC-related pathways. Conclusions: Collectively, our findings provide a system-level framework describing the associations between dysbiosis-relevant host pathways, CRC-related regulatory networks, and immune responses.<\/jats:p>","DOI":"10.3390\/jcm15187131","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:05:26Z","timestamp":1789391126000},"page":"7131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Multi-Omics Analysis Reveals Host Regulatory and Immune Networks with Inferred Dysbiosis Relevance in Colorectal Cancer"],"prefix":"10.3390","volume":"15","author":[{"given":"Huda","family":"Altoukhi","sequence":"first","affiliation":[{"name":"Radiotherapy Unit, Radiology Department, King Abdulaziz University Hospital, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Nawal H","family":"Siddig","sequence":"additional","affiliation":[{"name":"Department of Mathematical Sciences, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"given":"Nawal","family":"Al-Hoshani","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Mohammed Y.","family":"Refai","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Science, University of Jeddah, Jeddah 21493, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Fahd MF","family":"Aldowsari","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Science, University of Jeddah, Jeddah 21493, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Tariq","family":"Aziz","sequence":"additional","affiliation":[{"name":"Molecular Microbiology and Infectious Diseases Research Unit, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ionescu, V.A., Gheorghe, G., Bacalbasa, N., Chiotoroiu, A.L., and Diaconu, C. 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