Targeting Fusobacterium nucleatum in colorectal cancer: therapeutic strategies and future directions

There is growing evidence that Fusobacterium nucleatum, a Gram-negative anaerobic bacterium found in the gut and oropharynx, is a key player in the pathogenesis of colorectal cancer (CRC), by promoting tumor progression, immune evasion, and drug resistance. Despite the effectiveness of antibiotic regimens in reducing F. nucleatum abundance, concerns about antimicrobial resistance and gut dysbiosis limit the use of these drugs for a long period of time. Antimicrobial peptides (AMPs), bacteriophage therapy, and immune-based interventions all offer promising alternatives to conventional treatments. Checkpoint inhibitors and microbiome-based immunotherapy may also enhance antitumor immunity by alleviating F. nucleatum-induced immunosuppression. Furthermore, multimodal strategies, including dietary interventions and engineered probiotics, can help manage F. nucleatum-associated CRC holistically. It has been shown that probiotics can modulate gut microbiota composition and reduce F. nucleatum colonization by using strains of Lactobacillus and Bifidobacterium. This has led to improved outcomes for CRC patients by targeting this bacterium. In addition, preclinical evidence indicates that certain peptide-based antimicrobials can target F. nucleatum biofilms, though their specificity for pathogenic over commensal bacteria. Phage therapy, for instance, selectively targets the bacterium without harming others. But, to ensure efficacy and safety, clinical trials and mechanistic studies should be undertaken to optimize these therapeutic strategies. Understanding F. nucleatum's role in CRC and refining targeted interventions can help researchers develop innovative strategies to prevent and treat CRC. The purpose of this review is to examine current and emerging approaches to combating F. nucleatum in CRC, with a particular focus on probiotics, antibiotics, and alternative therapies.