摘要
Citrinin(CIT),a mycotoxin,is a secondary metabolite produced by Monascus.However,few studies have reported the physiological effects of CIT metabolites in vivo,particularly in conjunction with chronic ethanol exposure.In this study,the effects of CIT metabolites and injuries in Balb/c mice exposed to CIT for 28 d with/without ethanol co-exposure were investigated.Ethanol co-exposure caused gut barrier injury and a decrease in the levels of CIT and its metabolites in the gut.Meanwhile,CIT metabolites significantly increased in the liver,kidney,and hippocampus.Under co-exposure conditions,the length and density of intestinal villi in the mice were reduced,while concentrations of acetic acid and propionic acid were increased.CIT exposure significantly promoted a decrease in Lactobacillus and increases in Bacteroidetes,Prevotella,and Ruminococcus.While CIT alone had no significant effect on the hippocampus,co-exposure to CIT and alcohol induced hippocampus injury and exacerbated liver damage.Correlation analysis revealed an enhanced positive correlation between increased CIT metabolites and tryptophan metabolism,as well as alanine,aspartate,and glutamate metabolism pathways,and a negative correlation with purine metabolism and sulfur metabolism pathways,according to the gut-liverkidney and gut-liver-brain metabolic axes.Orotic acid and dimethyl sulfone served as biomarkers for coexposure-induced brain injury.These findings suggest that co-exposure enhances CIT metabolism,exacerbates injuries to the intestine,liver,kidney,and brain,and leads to metabolic disorders.
基金
supported by the National Key Research and Development Program of China(2022YFE0137500)
the Fundamental Research Funds for the Central Universities(JUSRP202401009,JUSRP222001)
the Key Laboratory of Biotoxin Analysis&Assessment for State Market Regulation(BAA202402)
the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province,Jiangnan University.
