Pathogenic Roles of Fusobacterium nucleatum in Colorectal Cancer: From Strain Heterogeneity to Host-Pathogen...

Area of Science:

• Microbiology
• Oncology
• Genomics

Background:

• Fusobacterium nucleatum (Fn) is a key tumor-associated pathogen in colorectal cancer (CRC).
• Fn exhibits significant heterogeneity at subspecies and clade levels, influencing its role in CRC.
• The F. nucleatum subsp. animalis C2 (Fna C2) lineage is a candidate high-risk clade with potential for enhanced tumor promotion.

Purpose of the Study:

• To review the lineage heterogeneity of Fn and its association with CRC.
• To explore host-pathogen interaction mechanisms underlying Fn's role in CRC.
• To discuss implications for lineage-resolved, context-aware frameworks in CRC research and clinical translation.

Main Methods:

• Literature review summarizing current evidence on Fn heterogeneity in CRC.
• Analysis of ecological enrichment, comparative genomics, and inferred metabolic features.
• Discussion of host-pathogen interactions, including adhesion, signaling, inflammation, immune suppression, and metabolism.

Main Results:

• Substantial heterogeneity exists within Fn, with specific lineages like Fna C2 showing potential for increased adaptability and tumor promotion.
• Fn contributes to CRC progression through multiple mechanisms, influenced by bacterial lineage, host, and microenvironment.
• Current evidence for Fna C2 relies mainly on indirect data, with limited direct clinical and mechanistic validation.

Conclusions:

• Moving beyond species-level associations to lineage-resolved and context-aware frameworks is crucial for understanding Fn's role in CRC.
• High-resolution stratification and risk classification based on Fn lineages could improve clinical translation.
• Further research is needed to validate the clinical significance and mechanistic basis of specific Fn lineages in CRC.