The Effects of Feeding ybfQ-Deficient Gut Bacteria on Radio-Tolerance in Symbiotic Caenorhabditis elegans: The Key Role of Isoscoparin.

It is inevitable for life on earth to be exposed to various types of ionizing and non-ionizing radiation, underscoring the importance of radioprotection. The symbiotic interaction between gut microbiota and the host provides a strategy for protecting the organism against these stressors. However, the genetic mechanisms underlying this interaction remain poorly understood due to the complexity and diversity of gut microbiota. In this study, we employed a symbiotic experimental system involving Caenorhabditis elegans and Escherichia coli to systemically investigate the effects of bacterial genetic alterations on host responses to radiation exposure. Our findings revealed that deletion of the bacterial ybfQ gene (ΔybfQ) significantly enhanced worm tolerance to UV-B radiation. Transcriptomic analysis demonstrated an enhanced antioxidant capacity in ΔybfQ-fed worms, as evidenced by reduced levels of reactive oxygen species (ROS) and restored oxidative homeostasis. Notably, ΔybfQ bacteria exhibited overproduction of isoscoparin, and exogenous supplementation with isoscoparin similarly enhanced worm radio-tolerance, underscoring its crucial role in ΔybfQ-mediated antioxidant of host worm. Both interventions retained their protective effects in IIS-deficient worms (daf-16). However, the protective effects of ΔybfQ feeding, but not isoscoparin treatment, were attenuated in daf-2 worms with a constitutively activated IIS pathway, accompanied by reduced bacteria gut colonization. Collectively, our results provide novel insights into the genetic basis of host-microbe interactions and propose a potential pharmacological strategy for radiation protection.