The Effects of a Modified Mediterranean Diet on Gut Microbiota and Chemotherapy Side Effects in Patients With Metastatic Colorectal Cancer Undergoing First-Line Chemotherapy With or Without Either Antiepidermal Growth Factor Receptor or Antivascular Endothelial Growth Factor Agent: Protocol for a Randomized Pilot Study in Italy
Bibliographic record
Abstract
BACKGROUND: The gut microbiota is attracting increasing interest as a factor possibly impacting colorectal cancer risk, therapy toxicity, and, as a consequence, patient's quality of life. It has been observed that microbial imbalance in the gut and in cancer tissue is facilitated by a Western type of diet, rich in meat, sugars, and refined grains, while a Mediterranean diet, rich in low saturated fat and fibers, promotes gut eubiosis, and results in reduced risk of developing colorectal cancer. Specifically, a high fiber content diet has been associated with a reduced incidence of therapy related adverse events in patients with malignant melanoma. OBJECTIVE: This study aimed to analyze and compare the gut microbiota of patients with metastatic colorectal cancer undergoing first-line chemotherapy with or without a biological agent (antiepidermal growth factor receptor or antivascular endothelial growth factor), and receiving either a free standard Western diet, or a modified Mediterranean diet, and the impact of microbiota on chemotherapy toxicity. METHODS: This is a pilot nondrug, interventional prospective, randomized, controlled, single-center (Italian), open-label trial. Patients (n=40) living in Italy, and with a local style of life, will be randomized 1:1 to either a modified Mediterranean diet or a free Western-type diet. Blood and fecal samples will be collected at baseline and control visits, for metagenomic and metabolomic analysis. The primary endpoint is the Firmicutes:Bacteroidetes ratio after completion of the third cycle of first-line chemotherapy (time T1). Secondary endpoints are (1) the percentage of patients experiencing gastrointestinal side effects at T1, (2) the percentage of patients experiencing grade 3/4 gastrointestinal side effects at T1, and (3) changes in the Firmicutes:Bacteroidetes ratio, overall microbiome composition, and metabolome at T1, and after the sixth chemotherapy cycle (T2) versus baseline. RESULTS: This pilot trial received ethics approval on July 24, 2024. By July 2025, a total of 17 participants have been recruited. The study will conclude with the visit at T2 for the last enrolled patient. Results are expected to be published in October 2028. CONCLUSIONS: This study has the potential to provide critical insights into the role of diet in modifying the gut microbiota, diminishing chemotherapy-related side effects, and possibly enhancing the therapeutic efficacy in metastatic colorectal cancer by improving tolerability. In addition, data may pave the way for future research in immunotherapy, potentially influencing both clinical practice and public health strategies. TRIAL REGISTRATION: Clinicaltrial.gov NCT06794931; https://clinicaltrials.gov/search?term=NCT06794931. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/72950.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.015 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".