Metagenome-metabolome responses to linarin alleviate hepatic inflammatory response, oxidative damage, and apoptosis in an ETEC-challenged weaned piglet model

Enterotoxigenic Escherichia coli (ETEC), present in contaminated food, water, and environments, can induce hepatic injury via the gut-liver axis, posing a serious threat to ecological systems and public health. Linarin, a flavonoid extracted from Chrysanthemum indicum, exhibits anti-inflammatory and antioxidant properties, but its protective effects against ETEC-induced hepatic injury remain unclear. In this study, 24 weaned piglets were randomly assigned to four groups: BD+NB (basal diet + nutrient broth), LN+NB (basal diet + 150 mg/kg linarin + nutrient broth), BD+ETEC (basal diet + ETEC challenge), and LN+ETEC (basal diet + 150 mg/kg linarin + ETEC challenge). Dietary linarin significantly increased ADFI and the genes related to oxidative damage and bile acid metabolism, while decreasing F:G ratio, liver index, serum liver function-related parameters, and the genes related to inflammatory response and apoptosis. It also significantly altered the relative abundances of gut microbiota, which were closely associated with key hepatic metabolic pathways, including nicotinate and nicotinamide metabolism and fatty acid biosynthesis. Our study suggests that linarin alleviated ETEC-induced hepatic inflammation and apoptosis, enhanced antioxidant capacity, and regulated bile acid metabolism. The potential mechanism involves linarin modulating gut microbiota-mediated key hepatic metabolic pathways to exert protective effects. In contrast to previous flavonoid-ETEC studies that primarily focused on the gut, this study, based on the gut-liver axis, investigates the potential mechanisms by which linarin is associated with the alleviation of ETEC-induced hepatic injury through integrated analysis of gut microbiome metagenomics and liver metabolomics.