title: Intestinal microbial variation may predict early acute rejection after liver transplantation in rats.
abstract: BACKGROUND
  Acute rejection (AR) remains a life-threatening complication after orthotopic liver transplantation (OLT) and there are few available diagnostic biomarkers clinically for AR. This study aims to identify intestinal microbial profile and explore potential application of microbial profile as a biomarker for AR after OLT.
  
  
  METHODS
  The OLT models in rats were established. Hepatic graft histology, ultrastructure, function, and intestinal barrier function were tested. Ileocecal contents were collected for intestinal microbial analysis.
  
  
  RESULTS
  Hepatic graft suffered from the ischemia-reperfusion (I/R) injury on day 1, initial AR on day 3, and severe AR on day 7 after OLT. Real-time quantitative polymerase chain reaction results showed that genus Faecalibacterium prausnitzii and Lactobacillus were decreased, whereas Clostridium bolteae was increased during AR. Notably, cluster analysis of denaturing gradient gel electrophoresis (DGGE) profiles showed the 7AR and 3AR groups clustered together with 73.4% similarity, suggesting that intestinal microbiota was more sensitive than hepatic function in responding to AR. Microbial diversity and species richness were decreased during AR. Phylogenetic tree analysis showed that most of the decreased key bacteria belonged to phylum Firmicutes, whereas increased key bacteria belonged to phylum Bacteroidetes. Moreover, intestinal microvilli loss and tight junction damage were noted, and intestinal barrier dysfunction during AR presented a decrease of fecal secretory immunoglobulin A (sIgA) and increase of blood bacteremia, endotoxin, and tumor necrosis factor-α.
  
  
  CONCLUSIONS
  We dynamically detail intestinal microbial characterization and find a high sensitivity of microbial change during AR after OLT, suggesting that intestinal microbial variation may predict AR in early phase and become an assistant therapeutic target to improve rejection after OLT.
authors.affiliation: 1 Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. 2 Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. 3 State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. 4 Correspondence to: Lin Zhou, M.D., Ph.D., First Affiliated Hospital, School of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou, China. 5 Correspondence to: Shusen Zheng, M.D., Ph.D., First Affiliated Hospital, School of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Ren
authors.forename: Jianwen
authors.initials: J
authors.lastname: Jiang
authors.forename: Haifeng
authors.initials: H
authors.lastname: Lu
authors.forename: Xinhua
authors.initials: X
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Haiyang
authors.initials: H
authors.lastname: Xie
authors.forename: Weilin
authors.initials: W
authors.lastname: Wang
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000208:Acute Disease; D000818:Animals; D058645:Denaturing Gradient Gel Electrophoresis; D006084:Graft Rejection / Q000209:etiology* / Q000382:microbiology; D007422:Intestines / Q000382:microbiology*; D016031:Liver Transplantation / Q000009:adverse effects*; D010802:Phylogeny; D011917:Rats, Inbred Lew; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D051193:Toll-Like Receptors