Bacteria pyruvate metabolism modulates AFB1 toxicity in Caenorhabditis elegans

Abstract

Aflatoxin B₁ (AFB₁), the most potent mycotoxin and Group 1 human carcinogen, continues to pose a significant public health burden, particularly in developing countries. Increasing evidence has shown the gut microbiota as a key mediator of AFB₁ toxicity through multiple interactive host-microbiota activities. In our previous study we observed that disturbances in bacterial pyruvate metabolism might have a significant impact on AFB₁ in the host. To further investigate the impact of the pyruvate pathway on AFB₁ toxicity in C. elegans, we engineered two bacterial strains (triple-overexpressed and triple-knockout strains with aceB, lpd, and pflB). Additionally, we employed two mutant worm strains (pyk-1 and pdha-1 mutants) known to affect pyruvate metabolism. Our results revealed that the co-metabolism of pyruvate by the host and bacterial strains synergistically influences AFB₁ toxicity. Remarkable, we found that bacterial pyruvate metabolism, rather than that of the host, plays a pivotal role in modulating AFB₁ toxicity in C. elegans. Our study sheds light on the role of gut microbiota involved in pyruvate metabolism in influencing AFB₁ toxicity in C. elegans.

Keywords: Aflatoxin B(1); C. elegans; Engineered bacteria; Host-microbe-chemical interaction; Pyruvate metabolic pathway.