Beyond Taxonomy: Fungal Nutraceutical Supplementation Modifies the Functional Potential of the Gut Microbiome in Colorectal Cancer
8 affiliations
- 1Microbiology and Infectology Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), 36312 Vigo, Spain
- 2Functional Biology and Health Sciences Department, Universidade de Vigo, 36310 Vigo, Spain
- 3Hifas da Terra S.L., 36154 Pontevedra, Spain
- 4Research Group in Gastrointestinal Oncology Disease in Ourense, 32005 Ourense, Spain
- 5Department of Gastroenterology, Hospital Universitario de Ourense, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 32005 Ourense, Spain
- 6Escuela Técnica Superior de Ingeniería (ETSE), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
- 7Microbiology Department, Complexo Hospitalario Universitario de Vigo (CHUVI), 36312 Vigo, Spain
- 8Department of Gastroenterology, Complexo Hospitalario Universitario de Vigo, 36312 Vigo, Spain
Abstract
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® 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® supplementation was associated with changes in the functional potential of the gut microbiome. A total of 37 patients were analyzed, including 24 receiving Micodigest® and 13 receiving placebo, with paired samples collected before supplementation and after 4–6 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®-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–Ljungdahl 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® may promote coordinated remodeling of the gut microbiome and host–microbiota 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.
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BibTeX
@article{rodriguezcostas2026beyond,
title = {{Beyond Taxonomy: Fungal Nutraceutical Supplementation Modifies the Functional Potential of the Gut Microbiome in Colorectal Cancer}},
author = {Nahir Rodríguez-Costas and Arturo Rodríguez-Blanco and Cristina Regueiro Expósito and Joaquín Cubiella and Esteban Sinde Stompel and Catalina Fernández-de-Ana Portela and Astrid Irene Diez Martín and Pablo Taboada-Rodríguez and Belén Fontán Silva and María Dolores Rodríguez Fernández and Sara Zarraquiños and David Remedios and Cristina Alejandra Sánchez Gómez and Sara Alonso Lorenzo and Romina Fernández Poceiro and María Luisa de Castro Parga and Vicent Hernández Ramírez and Sonia Pérez-Castro},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198936},
url = {https://www.mdpi.com/1422-0067/27/19/8936},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Beyond Taxonomy: Fungal Nutraceutical Supplementation Modifies the Functional Potential of the Gut Microbiome in Colorectal Cancer
AU - Nahir Rodríguez-Costas
AU - Arturo Rodríguez-Blanco
AU - Cristina Regueiro Expósito
AU - Joaquín Cubiella
AU - Esteban Sinde Stompel
AU - Catalina Fernández-de-Ana Portela
AU - Astrid Irene Diez Martín
AU - Pablo Taboada-Rodríguez
AU - Belén Fontán Silva
AU - María Dolores Rodríguez Fernández
AU - Sara Zarraquiños
AU - David Remedios
AU - Cristina Alejandra Sánchez Gómez
AU - Sara Alonso Lorenzo
AU - Romina Fernández Poceiro
AU - María Luisa de Castro Parga
AU - Vicent Hernández Ramírez
AU - Sonia Pérez-Castro
PY - 2026
DA - 2026/10/08
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27198936
UR - https://www.mdpi.com/1422-0067/27/19/8936
AB - 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® 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® supplementation was associated with changes in the functional potential of the gut microbiome. A total of 37 patients were analyzed, including 24 receiving Micodigest® and 13 receiving placebo, with paired samples collected before supplementation and after 4–6 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®-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–Ljungdahl 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® may promote coordinated remodeling of the gut microbiome and host–microbiota 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.
SN - 1422-0067
ER -