Preoperative metronidazole treatment to evaluate its efficacy in reducing Fusobacterium nucleatum colonisation in colorectal cancer patients: a proof-of-concept trial

Abstract

Background

Colorectal cancer (CRC) is one of the most prevalent tumour types and a leading cause of cancer-related mortality worldwide. Surgery represents the primary therapeutic option, while advanced cases are typically managed with established chemotherapy protocols, which exhibit variable response rates. Recently, the gut microbiota has been implicated in chemoresistance. Notably, Fusobacterium nucleatum, a commensal bacterium found in the oral cavity, is enriched in CRC tissues and has been shown in experimental models to promote CRC cell proliferation and diminish tumour responsiveness to 5-fluorouracil. Though the administration of metronidazole has effectively reduced F. nucleatum load and overall tumour growth in animal models, its efficacy in decreasing F. nucleatum loads in human CRC has yet to be verified.

Aim

This proof-of-concept trial aims to determine the effectiveness of metronidazole in reducing the F. nucleatum load in tissues and its potential detrimental effects on tumour cells and the tumour microenvironment.

Trial design

Forty patients newly diagnosed with CRC, for whom surgical resection is planned, will receive metronidazole for 10 days before surgery, which must be scheduled within 3 days following the last administration. Patients who do not receive the treatment for at least 7 days will be deemed ineligible for the study and will be replaced. Fusobacterium nucleatum abundance will be assessed through specific quantitative PCR analysis on genomic DNA extracted from diagnostic biopsies and excised tissues, with comparative analysis.