To investigate the effect of liver-specific knockdown of ANGPTL8 on the structure of the gut microbiota. We constructed mice with liver-specific ANGPTL8 knockdown by using an adeno-associated virus serotype 8 (AAV8) system harbouring an ANGPTL8 shRNA. We analysed the structure and function of the gut microbiome through pyrosequencing and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional prediction. Compared with controls, ANGPTL8 shRNA reduced the Simpson index and Shannon index (p < 0.01) of the gut microbiota in mice. At the phylum level, the sh-ANGPTL8 group showed a healthier gut microbiota composition than controls (Bacteroidetes: controls 67.52%, sh-ANGPTL8 80.75%; Firmicutes: controls 10.96%, sh-ANGPTL8 8.58%; Proteobacteria: controls 9.29%, sh-ANGPTL8 0.98%; F/B ratio: controls 0.16, sh-ANGPTL8 0.11). PCoA and UPGMA analysis revealed a significant difference in microbiota composition, while KEGG analysis revealed a significant difference in microbiota function between controls and the sh-ANGPTL8 group. Our results revealed that inhibition of ANGPTL8 signalling altered the structure of the gut microbiome, which might further affect the metabolism of mice. We have thus identified ANGPTL8 as a novel hepatogenic hormone potentially involving the liver-gut axis and regulating the structure of the gut microbiota.

中文翻译：

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肝脏特异性敲除ANGPTL8会改变小鼠肠道菌群的结构

研究肝脏特异性敲除ANGPTL8对肠道菌群结构的影响。我们通过使用带有ANGPTL8 shRNA的腺相关病毒血清型8（AAV8）系统构建了具有肝脏特异性ANGPTL8敲低的小鼠。我们通过焦磷酸测序和KEGG（基因和基因组京都百科全书）功能预测分析了肠道微生物组的结构和功能。与对照组相比，ANGPTL8 shRNA降低了小鼠肠道菌群的Simpson指数和Shannon指数（p <0.01）。在门上，sh-ANGPTL8组的肠道菌群组成比对照组更健康（拟杆菌：对照组67.52％，sh-ANGPTL8 80.75％;硬毛虫：对照组10.96％，sh-ANGPTL8 8.58％;变形杆菌：对照组9.29％，sh -ANGPTL8 0.98％； F / B比：对照0.16，sh-ANGPTL8 0.11）。PCoA和UPGMA分析揭示了微生物群组成的显着差异，而KEGG分析揭示了对照组和sh-ANGPTL8组之间微生物群功能的显着差异。我们的结果表明，对ANGPTL8信号的抑制改变了肠道微生物组的结构，这可能进一步影响小鼠的代谢。因此，我们已经确定ANGPTL8是一种潜在的涉及肝肠轴并调节肠道菌群结构的新型肝激素。