Engineering bifidobacteria to deliver CRISPR antimicrobials targeting oncogenic Fusobacterium nucleatum in colorectal tumors

Muhammad Shahid Mehmood; Tayyaba Qamar; Fatima Amjad; Naseeb Danaf

doi:10.1097/MS9.0000000000004437

Engineering bifidobacteria to deliver CRISPR antimicrobials targeting oncogenic Fusobacterium nucleatum in colorectal tumors

Ann Med Surg (Lond). 2025 Dec 3;88(1):40-41. doi: 10.1097/MS9.0000000000004437. eCollection 2026 Jan.

Authors

Muhammad Shahid Mehmood¹, Tayyaba Qamar¹, Fatima Amjad¹, Naseeb Danaf²

Affiliations

¹ Faculty of Veterinary Science, Institute of Microbiology, University of Agriculture Faisalabad, Faisalabad, Pakistan.
² Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon.

Abstract

Fusobacterium nucleatum (Fn) is increasingly recognized as a clinically meaningful driver in colorectal cancer (CRC), with recent multi-cohort sequencing studies detecting Fn in 35-45% of tumors and levels approaching 50% in stage II-III cases. Meta-analyses including more than 4000 patients consistently link Fn positivity to higher recurrence risk, shorter overall survival, and reduced response to fluoropyrimidine-based chemotherapy. The Fna C2 lineage shows the strongest association with malignancy, appearing in 29.2% of CRC samples compared with 4.8% of healthy controls (P < 5.6 × 10^-15). Engineered Bifidobacterium strains, which naturally accumulate in tumor hypoxic zones at densities near 10⁷ CFU/g, provide a platform for delivering CRISPR antimicrobials capable of reducing targeted microbes by 95-99% in vivo. These findings support efforts to eliminate oncogenic Fn within CRC tumors using precision microbial therapeutics.

Keywords: CRISPR antimicrobials; Fusobacterium nucleatum; colorectal cancer; engineered bifidobacterium; oncomicrobiome.

Publication types

Editorial