{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T07:47:28Z","timestamp":1791964048518,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Center for Industrial Technology Development, Madrid, Spain","award":["SOL-00105490"],"award-info":[{"award-number":["SOL-00105490"]}]},{"name":"Center for Industrial Technology Development, Madrid, Spain","award":["EXP00105490"],"award-info":[{"award-number":["EXP00105490"]}]},{"award":["SOL-00105490"],"award-info":[{"award-number":["SOL-00105490"]}],"id":[{"id":"https:\/\/ror.org\/0124x7055","id-type":"ROR","asserted-by":"publisher"}]},{"award":["EXP00105490"],"award-info":[{"award-number":["EXP00105490"]}],"id":[{"id":"https:\/\/ror.org\/0124x7055","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The gut microbiome is increasingly recognized as an important determinant of host immune regulation, intestinal homeostasis, and recovery after colorectal cancer (CRC) surgery. Although our previous randomized, double-blind, placebo-controlled clinical trial demonstrated that fungal nutraceutical supplementation with Micodigest\u00ae was associated with favorable taxonomic and systemic inflammatory changes in patients undergoing CRC surgery with curative intent, the functional consequences of this intervention remain poorly understood. Here, we performed a functional metagenomic analysis of fecal samples collected from patients enrolled in the original clinical trial to investigate whether Micodigest\u00ae supplementation was associated with changes in the functional potential of the gut microbiome. A total of 37 patients were analyzed, including 24 receiving Micodigest\u00ae and 13 receiving placebo, with paired samples collected before supplementation and after 4\u20136 weeks of intervention. Shallow shotgun metagenomic sequencing was performed, and microbial functional potential was characterized using KEGG Orthologues (KOs). Differential abundance analysis identified 14 significantly different KOs between groups at baseline and 23 after intervention, with no overlap between the two sets of orthologues. Following supplementation, Micodigest\u00ae-treated patients exhibited increased representation of functions related to CRISPR-associated systems, bacteriophage biology, and chitin-derived carbohydrate utilization, together with reduced representation of nutrient acquisition systems, conjugative transfer, sulfur metabolism, and components of the Wood\u2013Ljungdahl pathway. These functional signatures suggest coordinated changes in microbial ecological adaptation, nutrient utilization, genetic exchange, and metabolic activity following fungal nutraceutical supplementation. Integration with previously reported taxonomic and inflammatory findings supports the hypothesis that Micodigest\u00ae may promote coordinated remodeling of the gut microbiome and host\u2013microbiota interactions during the perioperative period. Although the present study cannot establish causality or directly infer microbial activity from metagenomic potential, these findings provide novel functional insights into the microbiome response to fungal nutraceutical supplementation in patients with CRC and highlight functional metagenomics as a valuable complement to taxonomic profiling.<\/jats:p>","DOI":"10.3390\/ijms27198936","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:40:17Z","timestamp":1791596417000},"page":"8936","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond Taxonomy: Fungal Nutraceutical Supplementation Modifies the Functional Potential of the Gut Microbiome in Colorectal Cancer"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5670-1898","authenticated-orcid":false,"given":"Nahir","family":"Rodr\u00edguez-Costas","sequence":"first","affiliation":[{"name":"Microbiology and Infectology Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), 36312 Vigo, Spain"},{"name":"Functional Biology and Health Sciences Department, \r\nUniversidade de Vigo, 36310 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3103-2710","authenticated-orcid":false,"given":"Arturo","family":"Rodr\u00edguez-Blanco","sequence":"additional","affiliation":[{"name":"Hifas da Terra S.L., 36154 Pontevedra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8567-6784","authenticated-orcid":false,"given":"Cristina Regueiro","family":"Exp\u00f3sito","sequence":"additional","affiliation":[{"name":"Research Group in Gastrointestinal Oncology Disease in Ourense, 32005 Ourense, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9994-4831","authenticated-orcid":false,"given":"Joaqu\u00edn","family":"Cubiella","sequence":"additional","affiliation":[{"name":"Research Group in Gastrointestinal Oncology Disease in Ourense, 32005 Ourense, Spain"},{"name":"Department of Gastroenterology, Hospital Universitario de Ourense, \r\nCentro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), 32005 Ourense, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban Sinde","family":"Stompel","sequence":"additional","affiliation":[{"name":"Hifas da Terra S.L., 36154 Pontevedra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0411-4382","authenticated-orcid":false,"given":"Catalina","family":"Fern\u00e1ndez-de-Ana Portela","sequence":"additional","affiliation":[{"name":"Hifas da Terra S.L., 36154 Pontevedra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8822-2991","authenticated-orcid":false,"given":"Astrid Irene Diez","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"Research Group in Gastrointestinal Oncology Disease in Ourense, 32005 Ourense, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0139-9951","authenticated-orcid":false,"given":"Pablo","family":"Taboada-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Escuela T\u00e9cnica Superior de Ingenier\u00eda (ETSE), \r\nUniversidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n Font\u00e1n","family":"Silva","sequence":"additional","affiliation":[{"name":"Microbiology Department, Complexo Hospitalario Universitario de Vigo (CHUVI), 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Dolores Rodr\u00edguez","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Microbiology Department, Complexo Hospitalario Universitario de Vigo (CHUVI), 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Zarraqui\u00f1os","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital Universitario de Ourense, \r\nCentro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), 32005 Ourense, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2682-0317","authenticated-orcid":false,"given":"David","family":"Remedios","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital Universitario de Ourense, \r\nCentro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), 32005 Ourense, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0924-2295","authenticated-orcid":false,"given":"Cristina Alejandra S\u00e1nchez","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital Universitario de Ourense, \r\nCentro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), 32005 Ourense, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Alonso","family":"Lorenzo","sequence":"additional","affiliation":[{"name":"Research Group in Gastrointestinal Oncology Disease in Ourense, 32005 Ourense, Spain"},{"name":"Department of Gastroenterology, Complexo Hospitalario Universitario de Vigo, 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina 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