Magnolol (MAG) exhibits hepatoprotective activity, however, whether and how MAG regulates the gut microbiota to alleviate fatty liver hemorrhagic syndrome (FLHS) remains unclear. Therefore, we investigated the mechanism of MAG in FLHS laying hens with an emphasis on alterations in the gut–liver axis. We randomly divided 540 56-week-old Hy-line white laying hens with FLSH into 4 groups. The birds were fed a high-fat low-protein (HFLP) diet (CON) or HELP diets supplemented with 200, 400, and 600 mg/kg of MAG (M1, M2, and M3, respectively) for 9 weeks. Magnolol supplementation increased the laying rate and ameliorated hepatic damage and dysfunction by regulating lipid metabolism, improving intestinal barrier function, and shaping the gut microbiota and tryptophan metabolic profiles. Dietary MAG supplementation downregulated the expression of lipid synthesis genes and upregulated the expression of lipid transport genes at varying degrees. The intestinal barrier function was improved by 200 and 400 mg/kg of MAG supplementation, as evidenced by the increased villus height and mRNA expression of tight junction related genes. Microbiological profile information revealed that MAG changed the gut microbiota, especially by elevating the abundances of Lactobacillus, Faecalibacterium, and Butyricicoccus. Moreover, non-targeted metabolomic analysis showed that MAG significantly promoted tryptophan metabolites, which was positively correlated with the MAG-enriched gut microbiota. The increased tryptophan metabolites could activate aryl hydrocarbon receptor (AhR) and relieved hepatic inflammation and immune response evidenced by the downregulated the gene expression levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the liver. The fecal microbiota transplantation (FMT) experiments further confirmed that the hepatoprotective effect is likely mediated by MAG-altered gut microbiota and their metabolites. Magnolol can be an outstanding supplement for the prevention and mitigation of FLHS in laying hens by positively regulating lipid synthesis and transport metabolism, improving the intestinal barrier function, and relieving hepatic inflammation by reshaping the gut microbiota and metabolite profiles through gut microbiota-indole metabolite-hepatic AhR crosstalk. These findings elucidate the mechanisms by which MAG alleviates FLHS and provide a promising method for preventing liver diseases by modulating gut microbiota and their metabolites.

中文翻译：

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厚朴酚通过塑造肠道微生物群和色氨酸代谢特征对脂肪肝出血综合征母鸡的肝脏保护作用


厚朴酚 (MAG) 具有保肝活性，但 MAG 是否以及如何调节肠道微生物群以减轻脂肪肝出血综合征 (FLHS) 仍不清楚。因此，我们研究了 FLHS 蛋鸡中 MAG 的机制，重点是肠-肝轴的改变。我们将 540 只 56 周龄海兰白蛋鸡 FLSH 随机分为 4 组。这些鸡饲喂高脂肪低蛋白（HFLP）饮食（CON）或补充有 200、400 和 600 mg/kg MAG（分别为 M1、M2 和 M3）的 HELP 饮食 9 周。补充厚朴酚可通过调节脂质代谢、改善肠道屏障功能以及塑造肠道微生物群和色氨酸代谢谱来提高产蛋率并改善肝损伤和功能障碍。膳食MAG补充剂不同程度地下调脂质合成基因的表达并上调脂质转运基因的表达。补充 200 和 400 mg/kg 的 MAG 可以改善肠道屏障功能，绒毛高度和紧密连接相关基因 mRNA 表达增加就证明了这一点。微生物学信息显示，MAG 改变了肠道微生物群，特别是通过提高乳杆菌、粪杆菌和丁酸球菌的丰度。此外，非靶向代谢组学分析表明，MAG 显着促进色氨酸代谢，这与富含 MAG 的肠道微生物群呈正相关。 色氨酸代谢物增加可以激活芳基碳氢化合物受体（AhR）并减轻肝脏炎症和免疫反应，这通过下调促炎细胞因子如白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF）的基因表达水平来证明。 -α) 和肝脏中的白细胞介素 6 (IL-6)。粪便微生物群移植 (FMT) 实验进一步证实，肝脏保护作用可能是由 MAG 改变的肠道微生物群及其代谢物介导的。厚朴酚可以通过积极调节脂质合成和转运代谢、改善肠道屏障功能、通过肠道菌群-吲哚代谢物重塑肠道菌群和代谢物谱来缓解肝脏炎症，从而成为预防和缓解蛋鸡 FLHS 的优秀补充剂。肝脏 AhR 串扰。这些发现阐明了 MAG 缓解 FLHS 的机制，并为通过调节肠道微生物群及其代谢物来预防肝病提供了一种有前景的方法。