Liver-specific knockdown of ANGPTL8 alters the structure of the gut microbiota in mice
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Cheng et al. Annals of Microbiology (2020) 70:58 https://doi.org/10.1186/s13213-020-01599-0
ORIGINAL ARTICLE
Open Access
Liver-specific knockdown of ANGPTL8 alters the structure of the gut microbiota in mice Yinlong Cheng1,2†, Yining Li1,2†, Yonghong Xiong1,2†, Yixin Zou1,2†, Siyu Chen1,2, Wenxiang Zhang1,2, Chang Liu1,2 and Yujie Shi1,2*
Abstract Purpose: To investigate the effect of liver-specific knockdown of ANGPTL8 on the structure of the gut microbiota. Methods: 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. Results: 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-ANGP TL8 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. Conclusion: 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. Keywords: ANGPTL8, Gut microbiota, Pyrosequencing, KEGG functional prediction
Introduction Incredible amounts of microorganisms exist in the human intestinal tract, the population of which reaches 100 trillion, far more than other microorganisms on the human surface, approximately 10 times the sum of both somatic cells and germ cells (Backhed et al. 2005). There are multifarious factors, especially those related to diet, involved in the regulation of the gut microbiota. It has been reported that specific diets or nutrients are beneficial or deleterious to the equilibrium of the gut * Correspondence: [email protected] † Yinlong Cheng, Yining Li, Yonghong Xiong and Yixin Zou contributed equally to this work. 1 State Key Laboratory of Natural Medicines, China Pharmaceutical University, No.639 Longmian Ave., Jiangning District, Nanjing 210098, Jiangsu, China 2 School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
microbiota. For instance, prebiotic, resistant starch and dietary polyphenols revealed the capacity to improve the host’s metabolic status and reduce the risks of chronic diseases, while high-fat diet (HFD) exacerbated dysbiosis of the gut microbiota and was involved in inflammatory processes (Sanchez-Tapia et al. 2019; Singh et al. 2018; Gowd et al. 2019). Diet i
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