Gut Microbiota In Chronic HBV Infection And Treatment Of HBeAg Negative Chronic Hepatitis B With Fecal Microbiota Transplantation

Gut microbiota affects the health of the human body greatly.Liver and gut are closely related and interact.Around 650 thousand people die from liver failure,cirrhosis and hepatocellular carcinoma caused by HBV infection every year.Fecal Microbiota Transplantation(FMT)induces HBeAg clearance in HBeAg positive chronic hepatitis B after long-term antiviral therapy.However,the mechanism how FMT induces HBV decline is unclear.It is important to find out the characteristics of gut microbiota in chronic HBV infection and the mechanism of FMT in the treatment of chronic hepatitis B to figure out a new way treating chronic HBV infection.In the first part of this study,we collected fecal samples from the health,HBeAg negative chronic HBV infection,HBeAg negative chronic hepatitis B,HBeAg positive chronic hepatitis B and cirrhosis after hepatitis B to undergo 16S rDNA sequencing for further analysis of gut microbiota.We found that gut microbiota between chonic HBV infection is significantly different from the health.The diversity of species in gut microbiota from HBeAg positive chronic hepatitis B and cirrhosis after hepatitis B group is decreased compared to the health.Coriobacteriaceae,Streptococcus and TM7-3 in HBeAg negative chronic HBV infection and HBeAg negative chronic hepatitis B were higher than the health.Streptococcus,Veillonella,Enterobacteriaceae and Haemophilus in decompensation cirrhosis after hepatitis B were increased compared to the health accompanied with the decrease of Clostridiaceae,Phascolarctobacterium,Coprococcus and Ruminococcaceae.In the second part of the study,we transplant the gut microbiota from healthy donors to HBeAg negative chronic hepatitis B patients after long-term antiviral.And we found that FMT could induce serum HBsAg decline up to 55.27%accompanied with serum endotoxin decline and gut microbiota transformation towards the donors.The proportion of Streptococcus,Clostridium,Clostridiaceae,Blautia,Coprococcus and Megamonas decreased significantly after FMT towards the level in gut microbiota from the donors.The proportion of Bacteroides,Butyricimonas,Odoribacter,Prevotella,Parabacteroides,Anaerostipes,Oscillospira,Ruminococcaceae and Sutterella increased significantly after FMT towards the level in gut microbiota from the donors.This study analyses the gut microbiota from chronic HBV infection and HBeAg negative chronic hepatitis B response to FMT to find out the relationship between gut microbiota,serum endotoxin and HBsAg decline.Preliminary revealed bacteria in genus with significant difference may contribute to HBsAg decline in patients.Serum HBsAg decline,endotoxin decline is related to the change of gut microbiota after FMT were figured out first time.This study provided a part of theory for the treatment of chronic HBV infection by FMT.