Intratumoral Fusobacterium nucleatum metabolizes chemotherapy before it reaches cancer cells

Fusobacterium nucleatum (Fn) has emerged as a crucial microbial determinant of chemotherapeutic failure in colorectal cancer. Detected in nearly 50% of all colorectal tumors, its presence is consistently associated with poorer prognosis and higher recurrence rates. Recent translational studies demonstrate that Fn metabolically interferes with cytotoxic drugs such as 5-fluorouracil and oxaliplatin, reducing active drug availability by up to 45%. This bacterium expresses nitroreductases and oxidoreductases capable of enzymatic inactivation, while its dense biofilms further hinder drug diffusion within the tumor microenvironment. Experimental depletion of Fn restores intratumoral drug levels and enhances tumor regression by approximately 60%, underscoring its direct role in metabolic resistance. Clinically, Fn-positive patients show diminished chemotherapy response and heightened inflammatory profiles. These findings collectively highlight that intratumoral microbiota, particularly Fn, can metabolize or neutralize chemotherapeutics before they reach cancer cells, an overlooked mechanism that challenges current cancer treatment paradigms.