State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong 510642, PR China; Guangdong provincial key laboratory for the development biology and environmental adaptation of agricultural organisms, Guangzhou, Guangdong 510642, PR China.
Guangdong Provincial Key Laboratory of Animal Nutrition and Regulation, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, PR China.
Poult Sci. 2024 Nov;103(11):104221. doi: 10.1016/j.psj.2024.104221. Epub 2024 Aug 16.
Zearalenone (ZEN), a mycotoxin produced by Fusarium species, is known for its reproductive toxicity as an estrogen analogue. However, there are limited knowledge about its hepatointestinal toxicity, as well as the role that gut microbiota and metabolites play in this process. In this study, a total of 24 thirty-week-old hens were fed to investigate the hepatointestinal toxicity subjected to long-term ZEN consumption at 2.0 mg/kg for 90 d. And we employed uncultured 16S rRNA sequencing for gut microbiota and untargeted metabolomics for fecal metabolites assessment. Notably, ZEN induced significant hepatic damage, as evidenced by hepatocyte necrosis, inflammatory cell infiltrate, increased liver lipopolysaccharide (LPS) and blood aspartate aminotransferase (AST) levels (P < 0.05). The decreased villus height, disruption of simple columnar epithelial cells, and exposure of the mucosal intrinsic layer were observed in the intestine. The gut microbial community composition and metabolites differed between ZEN group and control group. ZEN group exhibited higher gut microbial diversity (P < 0.05), lower Firmicutes/Bacteroidetes ratio and Lactobacillus abundance, and higher abundance in the genus such as Bacteroidetes, Parabacteroidetes and Desulfovibrio. Metabolomic analysis showed that ZEN treatment altered biosynthesis of siderophore group nonribosomal peptides and phenylpropanoids, metabolism of amino acid, digestion and absorption of vitamin and ABC transporters. Differential metabolites suggested that ZEN increase the risk of estrogen disorder, nucleic acid degradation, intestinal oxidative stress and inflammation. Neural network analysis showed that Ruminococcus was positively correlated with glyceric acid, and Prevotella was positively correlated with phenylacetylglycine. Both metabolites were positively correlated with blood AST level (P < 0.05), suggesting that intestinal microbe Ruminococcus and Prevotella might exacerbate liver damage by producing these harmful metabolites. Overall, we conclude that ZEN has damaged hepatointestinal system and the altered gut microbiota with resultant metabolite changes contribute to the adverse hepatointestinal effects of ZEN on laying hens. This study underscores the need for monitoring and mitigating ZEN exposure in poultry diets, highlighting its broader implications for animal health and food safety.
玉米赤霉烯酮（ZEN）是一种由镰刀菌属产生的真菌毒素，因其作为雌激素类似物具有生殖毒性而闻名。然而，关于其肝肠毒性以及肠道微生物群和代谢物在这一过程中所起的作用，人们知之甚少。在这项研究中，我们共使用了 24 只 30 周龄的母鸡，以研究在 2.0mg/kg 下长期（90 天）摄入 ZEN 对其产生的肝肠毒性。我们采用未培养的 16S rRNA 测序来评估肠道微生物群，采用非靶向代谢组学来评估粪便代谢物。值得注意的是，ZEN 导致了显著的肝损伤，表现为肝细胞坏死、炎症细胞浸润、肝内脂多糖（LPS）和血液天门冬氨酸氨基转移酶（AST）水平升高（P<0.05）。在肠道中，还观察到绒毛高度降低、简单柱状上皮细胞破坏和黏膜固有层暴露。ZEN 组和对照组的肠道微生物群落组成和代谢物存在差异。ZEN 组表现出更高的肠道微生物多样性（P<0.05），更低的Firmicutes/Bacteroidetes 比值和乳杆菌丰度，以及更高丰度的拟杆菌门、Parabacteroidetes 门和脱硫弧菌属。代谢组学分析表明，ZEN 处理改变了铁载体非核糖体肽和苯丙氨酸类的生物合成、氨基酸代谢、维生素消化和吸收以及 ABC 转运体。差异代谢物表明，ZEN 增加了雌激素紊乱、核酸降解、肠道氧化应激和炎症的风险。神经网络分析表明，瘤胃球菌与甘油酸呈正相关，普雷沃氏菌与苯乙酰甘氨酸呈正相关。这两种代谢物与血液 AST 水平呈正相关（P<0.05），这表明肠道微生物瘤胃球菌和普雷沃氏菌可能通过产生这些有害代谢物加剧肝脏损伤。总的来说，我们得出结论，ZEN 损害了肝肠系统，而改变的肠道微生物群及其产生的代谢物变化导致了 ZEN 对产蛋鸡的不良肝肠影响。这项研究强调了在禽饲料中监测和减轻 ZEN 暴露的必要性，突显了其对动物健康和食品安全的更广泛影响。
