Gut Microbiota and Gut Environment in Non-Compensated Liver Failure: A Multifaceted Study Using a Rat Liver Transplant Model and Liver Transplant Patients

Abstract

Introduction: Few studies investigated the changes of intestinal bacteria associated with progressive liver failure and compared the differences/similarities of gut microbiota between species in disease models. The aim of this study was to confirm the universality of these changes in both small animal models and humans. Method: ① A rat allogeneic liver transplantation model was prepared, and changes in liver dysfunction, gut microbiota, fecal organic acid concentration, and bacterial translocation (BT) were observed in the absence of immunosuppressive drugs. The data were compared with the syngeneic model. ② We also collected stool and blood samples from adult recipients of living donor liver transplantation at our institution before transplantation and observed the same parameters as in rats. Donors were used as comparison subjects. Results: The allogeneic model died around day 11 due to acute cellular rejection. Both the allogeneic model at day 10 and human recipients showed marked dysbiosis compared to the control group. In particular, there was a decrease in several predominantly anaerobic bacteria and an increase in Enterobacteriaceae and Enterococcus. The concentration of fecal short-chain fatty acids was markedly reduced. In the allogeneic model, as rejection and liver failure progressed, immunocompetence decreased, intestinal barrier function decreased, and blood lipopolysaccharide increased. The same trend was observed in recipients, and the higher the MELD score, the more severe the dysbiosis, intestinal dysbiosis and BT. Conclusions: Under severe liver dysfunction, systemic immunity and intestinal barrier function were impaired, leading to dysbiosis of the intestinal microbiota and BT in both small animals and humans.