Multi-omics analysis of the gut-liver axis reveals the health hazards of embryonic egg exposure to zearalenone in chicks

Zearalenone (ZEN), a widespread Fusarium-derived mycotoxin, poses health risks to animals and humans through contaminated food chains. However, its transgenerational effects following embryonic egg exposure on avian development and chick health remain poorly characterized.This study employed embryonic egg injection and multi-omics approaches to evaluate the impacts of ZEN (0, 5, 50, or 500 μg/egg) administered to Hy-line Brown eggs on day 5 of incubation. ZEN exposure significantly decreased hatchability and initial chick weight. During the 20-day post-hatch period, it induced dose-dependent reductions in net weight, average daily gain, and average daily feed intake, while increasing the feed conversion ratio.Histopathology showed intestinal inflammation and structural damage, coupled with gut microbiota dysbiosis, notably an elevated abundance of pathogenic bacteria such as Escherichia coli. ZEN also caused liver injury, manifested by elevated serum biochemical indices, oxidative stress, and inflammatory responses. Hepatic metabolomics revealed pronounced alterations in metabolites and pathways associated with lipid metabolism, autophagy, and antioxidant defense.Correlation analyses indicated interconnections between gut microbiota dysbiosis and hepatic metabolic disturbances, suggesting mediation of ZEN developmental toxicity via the gut-liver axis. These results elucidate novel mechanisms of ZEN embryotoxicity and underscore the need to control ZEN contamination in poultry production.