Fungal nutraceutical supplementation with Micodigest® was associated with changes in the functional potential of the gut microbiome in colorectal cancer patients, including increased representation of 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.
Key Findings
Results
Differential abundance analysis identified 14 significantly different KEGG Orthologues (KOs) between Micodigest® and placebo groups at baseline, and 23 significantly different KOs after intervention, with no overlap between the two sets of orthologues.
A total of 37 patients were analyzed: 24 receiving Micodigest® and 13 receiving placebo.
Paired fecal samples were 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).
The absence of overlap between baseline and post-intervention differentially abundant KOs suggests the post-intervention differences were not driven by pre-existing group differences.
Results
Following Micodigest® supplementation, patients exhibited increased representation of functions related to CRISPR-associated systems and bacteriophage biology.
This finding was observed after 4-6 weeks of Micodigest® supplementation compared to placebo.
CRISPR-associated systems and bacteriophage biology functions were among the 23 significantly different KOs identified post-intervention.
The authors interpret these changes as suggesting coordinated changes in microbial ecological adaptation and genetic exchange following fungal nutraceutical supplementation.
These functional changes were not present at baseline, indicating they emerged during the supplementation period.
Results
Micodigest® supplementation was associated with increased representation of chitin-derived carbohydrate utilization functions in the gut microbiome.
Chitin-derived carbohydrate utilization was one of the functional categories showing increased representation after intervention in the Micodigest® group.
This finding was among the 23 significantly different KOs identified post-intervention.
Micodigest® is a fungal nutraceutical, and chitin is a primary structural component of fungal cell walls, suggesting a plausible biological mechanism.
This change was not observed at baseline, indicating it emerged as a consequence of the supplementation.
Results
Micodigest® supplementation was associated with reduced representation of nutrient acquisition systems, conjugative transfer, sulfur metabolism, and components of the Wood-Ljungdahl pathway.
These reductions were identified among the 23 significantly different KOs post-intervention.
The Wood-Ljungdahl pathway is a carbon fixation and acetogenic metabolic pathway used by certain anaerobic gut bacteria.
Conjugative transfer refers to horizontal gene transfer mechanisms between bacteria, and its reduction may reflect shifts in microbial community dynamics.
The authors suggest these changes reflect coordinated changes in nutrient utilization and metabolic activity following supplementation.
Methods
The study was a functional metagenomic re-analysis of a previously conducted randomized, double-blind, placebo-controlled clinical trial of Micodigest® in colorectal cancer surgery patients.
The original trial had previously demonstrated favorable taxonomic and systemic inflammatory changes associated with Micodigest® supplementation.
The intervention period was 4-6 weeks, with supplementation occurring perioperatively in patients undergoing CRC surgery with curative intent.
Sample size was 37 total patients (24 Micodigest®, 13 placebo), with paired pre- and post-intervention fecal samples.
The current analysis used shallow shotgun metagenomic sequencing rather than 16S rRNA amplicon sequencing, providing functional rather than solely taxonomic information.
Discussion
Integration of functional metagenomic findings with previously reported taxonomic and inflammatory data supports the hypothesis that Micodigest® may promote coordinated remodeling of the gut microbiome and host-microbiota interactions during the perioperative period.
The authors state the findings 'support the hypothesis that Micodigest® may promote coordinated remodeling of the gut microbiome and host-microbiota interactions during the perioperative period.'
The study cannot establish causality or directly infer microbial activity from metagenomic potential.
The functional signatures identified suggest changes across multiple microbial processes including ecological adaptation, nutrient utilization, genetic exchange, and metabolic activity.
The authors highlight functional metagenomics as 'a valuable complement to taxonomic profiling' in this context.
What This Means
This research suggests that taking a fungal supplement called Micodigest® for 4-6 weeks before and after colorectal cancer surgery can meaningfully change not just which bacteria live in the gut, but what those bacteria are capable of doing. The researchers analyzed stool samples from 37 patients (24 taking the supplement, 13 taking a placebo) using a technique called shotgun metagenomic sequencing, which reads the genetic material from all microbes in a sample and can identify their functional capabilities. They found 23 genetic functions that were significantly different between the supplemented and placebo groups after the intervention period — functions related to how bacteria defend themselves against viruses, how they share genetic information, how they digest chitin (a component of fungal cell walls), and how they carry out certain metabolic processes.
The specific changes observed after Micodigest® supplementation included increases in bacterial defense systems (CRISPR) and the ability to break down chitin-derived sugars, while there were decreases in certain nutrient-scavenging systems, mechanisms for sharing genes between bacteria, sulfur processing, and a particular carbon metabolism pathway (Wood-Ljungdahl). These changes did not overlap with any pre-existing differences between groups at baseline, suggesting the supplement itself drove the functional shifts rather than pre-existing differences between patients.
This research matters because it goes beyond simply cataloging which bacteria are present in the gut and begins to reveal what those bacteria are functionally doing differently in response to fungal supplementation. The study builds on a prior clinical trial that had already shown favorable changes in bacterial composition and inflammation markers, and the authors suggest these functional changes may help explain how the supplement supports the gut ecosystem during the stressful period surrounding cancer surgery. However, the researchers caution that this type of analysis identifies genetic potential rather than confirmed microbial activity, and the study cannot prove that Micodigest® directly caused these effects.
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Rodríguez-Costas N, Rodríguez-Blanco A, Expósito C, Cubiella J, Stompel E, Fernández-de-Ana Portela C, et al.. (2026). Beyond Taxonomy: Fungal Nutraceutical Supplementation Modifies the Functional Potential of the Gut Microbiome in Colorectal Cancer.. International journal of molecular sciences. https://doi.org/10.3390/ijms27198936