Analysis Of Dynamic Gut Microbiota In Mice With Intestinal Epithelium Specific Deficiency Of Autophagy Gene Atg5/Atg7 Using Metagenomic Technology

Autophagy, one kind of programmed cell death, is seen in a variety of animal tissues and organs with widely function. On one hand, it degraded intracellular proteins and produced nutrition for host survival and development. On the other hand, it can protect host from pathogens by phagocytosis. Atg5, Atg7, two important genes which involved autuphagic pathway, are engaged in ubiquitination pathway and play essential role in forming autophagosome.Gut microbiota is enriched in animal intestine, which engaged in host nutrition, metabolism and immunity, especially for the intestine. It has been proved that gut microbiota has function associated with damage or protect intestinal immune barrier directly to affect host immunity. However, the relationship between autophagy and gut microbiota is still blurry.In this study, we investigated the relationship of autophagy and gut microbiota. We developed mice model with intestinal epithelium specific deficiency of Atg5/Atg7 and detected changes of autophagy in intestinal mucosal tissues. At the same time, we analyze the distribution of species and metabolic pathway of gut microbiota aided by next generation sequencing. Results showed that(1) After knockout of Atg5, Atg7, signal of autophagy was reduced along with the malformation of Paneth cell and immunoprotein MUC2 was increased. That indicated that we succeeded in developing mice model and lack of Atg5, Atg7 will induce responding of authophagic pathway and intestinal immune system.(2) Significant difference of gut microbiota composition was detected in deficiency mice compared to wild type. Further analysis found that significantly different species were associated with host metabolism and immune disease, such as Butyricicoccus pullicaecorum, which was common significant different species in Atg5, Atg7 and associated with immune bowel disease, indicated its relationship with host autophagy and immunity.(3) The functions of different gut microbiota between knockout and wild type mice were enriched in the pathway of transporter, genetic information transfer, and, nutrition metabolism, which indicated the interaction between autophagy and these microbial pathway.Our study confirmed the influence of autophagy on species composition of gut microbiota, which supported the conclusion that with host gene modification, gut microbiota will change correspondingly along with the molecular pathway. This research provided new view and crucial basis to discuss interaction of host and microbiota for coming study.