Intergenerational inheritance of quercetin-induced abnormal immunity in mice

Quercetin, a dietary flavonol enriched in food, regulates immune-related models through epigenetic modifications. However, few studies have explored the transmission of regulatory effects across generations to the progeny. Here, we selected <i>Escherichia coli</i>, a conditional pathogen capable of causing gastrointestinal infections or various localized tissue and organ infections under specific conditions, as the pathogenic strain to infect mice. We provide evidence that quercetin can not only induce responsiveness changes against systemic <i>E. coli</i> infection in directly exposed organisms, but also in subsequent generations through the transgenerational inheritance of epigenetic traits. Both parental male mice and their progeny exhibited cellular and phenotypic changes associated with metabolic alterations. Surprisingly, the male and female progeny of mice treated with quercetin (200 mg/kg) for six weeks negatively enhanced the survival rate under systemic <i>E. coli</i> (1 × 10⁸ CFU/mL) infection, concurrent with an increase in bacterial loads in the liver and spleen. Serum TNF-α and IL-1β levels significantly increased post-infection in the progeny. Our results provide the first evidence of the inheritance of immunity driven by quercetin in mammals and the attenuation of protection against bacterial infection.