Indole profiles define disease-specific virulence in Fusobacterium nucleatum clinical isolates

This study investigates the metabolic and virulence characteristics of Fusobacterium nucleatum clinical isolates collected from colorectal cancer (CRC), Crohn’s disease, healthy individuals, and oral lesion. Focusing on the microbial metabolite indole and its derivatives—produced via tryptophan metabolism—the research demonstrates that CRC-associated F. nucleatum isolates produce significantly higher levels of indole. These isolates also exhibit distinct biofilm formation capacities and altered expression of virulence genes (e.g., fap2, fadA, aid1, radD) in response to indole exposure. Using machine learning classification based on gene expression profiles, the study shows that indole responsiveness can predict disease origin of isolates. The findings suggest that indole metabolism represents a niche-specific adaptation in CRC-associated F. nucleatum, with implications for understanding microbial contributions to cancer pathogenesis and potential therapeutic targeting.