JMIR Publications

ABSTRACT

Background:

the gut microbiota is attracting increasing interest as an initiator of colorectal cancer. It has been observed that microbial imbalance in the gut and in cancer tissue is facilitated by a Western type 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.

Objective:

to analyze and compare the gut microbiota of patients with metastatic colorectal cancer undergoing first-line chemotherapy +/- a biological agent (anti-EGFR or anti-VEGF), and receiving either a free standard Western diet, or a modified Mediterranean diet.

Methods:

this is a pilot non-drug, interventional prospective, randomized, controlled, single-center, open-label trial. Patients (n=40) 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: a) the percentage of patients experiencing gastrointestinal side effects at T1; b) the percentage of patients experiencing grade 3/4 gastrointestinal side effects at T1; c) 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 has received ethics approval on July 24th 2024. By January 2025, 7 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. Additionally, data may pave the way for future research in immunotherapy, potentially influencing both clinical practice and public health strategies. Clinical Trial: Clinicaltrial.gov NCT06794931 (https://clinicaltrials.gov/search?term=NCT06794931)