Investigating the Impact of Fusobacterium nucleatum on Oxidative Stress, Chemoresistance, and Inflammation in Inflammatory Bowel Disease and Colorectal Cancer: Rationale and Design of a Clinical Trial

Fusobacterium nucleatum (F. nucleatum), a Gram-negative anaerobe, is increasingly implicated in the pathogenesis of colorectal cancer (CRC) and inflammatory bowel disease (IBD). Its adhesin FadA enables epithelial adherence and invasion, promoting inflammation and tumorigenesis. F. nucleatum has been shown to activate the NLRP3 inflammasome, leading to IL-1β release, and is associated with chemoresistance and poor prognosis in CRC. Additionally, lipid peroxidation markers such as malondialdehyde (MDA) and 4-hydroxy-nonenal (4-HNA) may contribute to inflammation-driven carcinogenesis. This study protocol aims to investigate the role of F. nucleatum in the development and progression of IBD and CRC through integrated clinical, molecular, and imaging approaches. The protocol involves quantifying F. nucleatum in tissue biopsies across disease stages and assessing correlations with inflammatory and oxidative markers. It will explore the bacterium’s involvement in NLRP3 inflammasome activation, IL-1β production, and autophagy, and its potential contribution to chemoresistance. Furthermore, radiomic analysis of computed tomography (CT) images will be performed to identify imaging phenotypes associated with microbial load and inflammatory activity. Although primarily a protocol, the study includes preliminary in vitro data showing that exposure to FadA significantly increases inflammatory markers in Caco-2 cells, supporting the hypothesis that F. nucleatum contributes to a pro-inflammatory, pro-tumorigenic microenvironment relevant to CRC progression.