Effects of gut microflora on hepatic damage after acute liver injury in rats.
BACKGROUND
Liver injury often causes disruption of the gut microflora. The aim of this work was to evaluate the effects of microflora variations on acute liver injury.


METHODS
Sprague-Dawley rats received saline, probiotics, Escherichia coli, Salmonella enteritidis, or gentamicin via daily gavage for 7 days. Acute liver injury was induced on the eighth day by intraperitoneal injection of d-galactosamine except for the normal group. Samples were collected 24 hours later. Bacterial translocation (BT) was evaluated from the liver, spleen, kidney, and mesenteric lymph nodes. Liver enzymes, histologic analysis, endotoxin, serum tumor necrosis factor-alpha, interleukin (IL)-6, IL-10, IL-12, CD3 and CD4 T cells in peripheral blood and Peyer's patches, intestinal bacteria, and intestinal mucosal ultrastructure were studied.


RESULTS
Orally administered probiotics, nonpathogenic E. coli, and gentamicin, respectively, markedly attenuated liver damage, decreased BT, and decreased the levels of serum tumor necrosis factor-alpha, IL-6, IL-10, and IL-12. Treatment with S. enteritidis had opposite results. Only orally supplemented S. enteritidis significantly affected the CD3 and CD4 T cells counts in peripheral blood and Peyer's patches.


CONCLUSIONS
We demonstrated that modifications in gut microflora had different effects on the prevention or exacerbation of acute liver injury. Moreover, alterations in gut microflora affected liver damage through three major factors: BT and the release of local gut cytokine and endotoxin.
Li
Yong-Tao
YT
From the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Wang
Li
L
Chen
Yu
Y
Chen
Yun-Bo
YB
Wang
Hua-Ying
HY
Wu
Zhong-Wen
ZW
Li
Lan-Juan
LJ
D000818:Animals; D018988:Bacterial Translocation; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004731:Endotoxins / Q000097:blood; D004926:Escherichia coli; D005688:Galactosamine; D005839:Gentamicins / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000473:pathology; D007422:Intestines / Q000382:microbiology*; D007668:Kidney / Q000382:microbiology; D008099:Liver / Q000201:enzymology / Q000382:microbiology; D008107:Liver Diseases / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D008198:Lymph Nodes / Q000382:microbiology; D008297:Male; D008643:Mesentery; D010581:Peyer's Patches; D019936:Probiotics / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012477:Salmonella enteritidis; D013154:Spleen / Q000382:microbiology
D016207:Cytokines; D004731:Endotoxins; D005839:Gentamicins; D005688:Galactosamine