(P12-016-25) A Novel Mechanism for Curcumin’s Cancer-Fighting Effects: A Genius Action of Gut Microbiota

Objectives: To investigate the role of gut microbiota in enhancing the anti-cancer properties of curcumin by producing its active metabolite, octahydrocurcumin (OHC), and to explore variability in OHC production among individuals.

Methods: Human stool samples were collected and subjected to fermentation and metabolite identification using untargeted metabolomic studies. The anti-cancer properties of OHC were evaluated and compared to curcumin using in vivo animal studies. Moreover, bacterial strains with OHC-producing capabilities were isolated and characterized using whole genome sequencing.

Results:

Significant inter-individual variation in OHC production was observed, with 40% of participants categorized as OHC producers. OHC demonstrated superior anti-cancer efficacy compared to curcumin. Notably, bacterial strains, including Escherichia coli and Lactobacillus gasseri, capable of 100% OHC transformation, were successfully isolated from human stool samples, highlighting their therapeutic and biotechnological potential.

Conclusions: The findings reveal the pivotal role of gut microbiota in curcumin bioactivation and its enhanced anti-cancer properties. The discovery of efficient OHC-producing bacteria opens avenues for personalized therapeutic interventions, such as fecal transplantation or co-delivery systems involving OHC-producing strains, to maximize the efficacy of curcumin-based treatments.

Funding Sources:

This work was partially funded by the National Institutes of Health and the United States Department of Agriculture (USDA NIFA grants and USDA Hatch Multistate).