Lv Yujie, Ge Chaoyue, Wu Lianchi, Hu Zhaoying, Luo Xinyu, Huang Weichen, Zhan Shenao, Shen Xinyu, Yu Dongyou, Liu Bing
Hainan Institute, Zhejiang University, 572000, Sanya, China.
College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China.
J Anim Sci Biotechnol. 2024 Sep 6;15(1):120. doi: 10.1186/s40104-024-01074-9.
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.
厚朴酚（MAG）具有肝脏保护活性，然而，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MAG在FLHS蛋鸡中的作用机制，重点关注肠-肝轴的变化。我们将540只56周龄患有FLSH的海兰白蛋鸡随机分为4组。这些鸡被喂食高脂低蛋白（HFLP）日粮（对照组）或分别添加200、400和600 mg/kg MAG的日粮（分别为M1、M2和M3），持续9周。
补充厚朴酚可提高产蛋率，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改善肝脏损伤和功能障碍。日粮中添加MAG不同程度地下调了脂质合成基因的表达，并上调了脂质转运基因的表达。补充200和400 mg/kg的MAG可改善肠道屏障功能，绒毛高度增加以及紧密连接相关基因的mRNA表达增加证明了这一点。微生物谱信息显示，MAG改变了肠道微生物群，特别是通过提高乳酸杆菌属、粪杆菌属和丁酸球菌属的丰度。此外，非靶向代谢组学分析表明，MAG显著促进色氨酸代谢产物，这与富含MAG的肠道微生物群呈正相关。色氨酸代谢产物的增加可激活芳烃受体（AhR），并减轻肝脏炎症和免疫反应，肝脏中促炎细胞因子如白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的基因表达水平下调证明了这一点。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。
厚朴酚可以通过积极调节脂质合成和转运代谢、改善肠道屏障功能以及通过肠道微生物群-吲哚代谢产物-肝脏AhR串扰重塑肠道微生物群和代谢谱来减轻肝脏炎症，从而成为预防和缓解蛋鸡FLHS的优秀补充剂。这些发现阐明了MAG减轻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景的方法。
