Using large-scale screening in C. elegans, along with validation in human cancer cells and a fly model of colorectal cancer, scientists demonstrated that 2-MiCit has potent anti-cancer properties and can extend survival in these model organisms.

An international team led by researchers from Imperial College London and the University of Cologne discovered that bacteria associated with tumors produce metabolites capable of influencing cancer progression and enhancing chemotherapy efficacy.

Microbiologist Himanshu Mishra from Zydus Lifescience emphasized the significance of microbiota-derived metabolites, particularly 2-methylisocitrate, in cancer therapy.

Scientists chemically modified 2-MiCit to create a synthetic version that showed even greater potency, pointing toward potential new drug development based on microbial metabolites.

Further chemical modification into a trimethyl ester form increased 2-MiCit’s therapeutic potency, suggesting microbiome-derived metabolites could serve as co-adjuvants in cancer treatment.

Multi-omic analyses revealed that 2-MiCit inhibits mitochondrial IDH, causing nucleotide imbalance and DNA damage, which hampers tumor growth.

The molecule’s mechanism involves inhibiting a key mitochondrial enzyme in cancer cells, leading to DNA damage and activation of pathways that slow cancer progression, working synergistically with 5-FU.

Researchers have identified a bacterial metabolite called 2-methylisocitrate (2-MiCit), produced by E. coli and tumor-associated microbiomes, which significantly enhances the effectiveness of the chemotherapy drug 5-fluorouracil (5-FU).

The study employed a comprehensive host-microbe-drug-nutrient screening approach, revealing that 2-MiCit is produced and enriched in human tumor microbiota and exhibits anti-proliferative effects across various cancer models.

Research indicates that cancer-associated microbiome metabolites can have dual effects, both inhibiting tumor growth and influencing proliferation, which could be leveraged in therapy.

This metabolite works by influencing cellular pathways related to metabolism and DNA damage, thereby synergizing with 5-FU to improve its anti-cancer effects.

The findings underscore the role of the tumor microbiome in cancer progression and suggest that microbial metabolites like 2-MiCit could be harnessed to improve treatment outcomes, highlighting the importance of personalized medicine.