背景:厚朴酚(MAG)具有保肝活性,然而,MAG是否以及如何调节肠道菌群以缓解脂肪肝出血性综合征(FLHS)尚不清楚.因此,我们研究了MAG在FLHS蛋鸡中的作用机制,重点是肠-肝轴的改变。我们将540只56周龄的Hy线白色蛋鸡用FLSH随机分为4组。饲喂鸟类的高脂肪低蛋白(HFLP)饮食(CON)或HELP饮食,并补充了200、400和600mg/kg的MAG(分别为M1,M2和M3),持续9周。
结果:添加厚朴酚通过调节脂质代谢,提高产蛋率,改善肝功能损害和功能障碍,改善肠道屏障功能,并塑造肠道微生物群和色氨酸代谢谱。日粮补充MAG在不同程度上下调了脂质合成基因的表达,上调了脂质转运基因的表达。补充200和400mg/kg的MAG可改善肠道屏障功能,绒毛高度和紧密连接相关基因的mRNA表达增加证明了这一点。微生物概况信息显示,MAG改变了肠道微生物群,特别是通过提高乳酸菌的丰度,粪杆菌,和Butyricicocus。此外,非靶向代谢组学分析表明,MAG对色氨酸代谢产物有显著的促进作用,与富含MAG的肠道菌群呈正相关。色氨酸代谢产物的增加可以激活芳香烃受体(AhR),并通过下调促炎细胞因子如白细胞介素-1β(IL-1β)的基因表达水平来缓解肝脏炎症和免疫反应。肿瘤坏死因子-α(TNF-α),和白细胞介素-6(IL-6)在肝脏。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产物介导的。
结论:厚朴酚可以通过积极调节脂质合成和转运代谢来预防和缓解蛋鸡FLHS,改善肠道屏障功能,通过肠道微生物群-吲哚代谢物-肝AhR串扰重塑肠道微生物群和代谢物谱来缓解肝脏炎症。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产物预防肝脏疾病提供了一种有前途的方法。
BACKGROUND: 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.
RESULTS: 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.
CONCLUSIONS: 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.