Effects Of Gut Microflora On Hepatic Damage Following Acute Liver Injury And The Plasmic Metabolic Profiles In Rats

The human gut harbours a large and dynamic bacteria community which plays amajor role in human health.There are more than 800 species of microorganisms in thehuman intestine,but a substantial part of these bacteria populations are still to beevaluated.The effects of commensal microflora on host's physiology and pathologyhave been well documented.Most importmant of the which are promoting thematuration of intestinal immune system,protecting the host against colonizion byinvasive alien microbes and affecting the metabolism.Previous studies demonstratedthat following damage to the liver there was reduced blood flow through the gut-liveraxis,altered bile secretion and impaired peristaisis,leading to the disruption of themucosal barrier and the ecological balance of the gut microflora.The relationshipbetween the alteration of gut microflora and hepatic damage has not been addressed yet.In this study,we aimed to clarify the effect of changed microflora on acute liver injury.whether or not changes in gut microflora exacerbated liver damage on liver injury and the metabolism.The relationships betweenthe alteration of gut microflora and hepaticdamage as well as the metabolism have not been addressed yet.In this study,we aimedto clarify the effect of changedmicroflora on acute liver injury and the possiblemechanism(s)involved as well as the metabolism.Methods:Part 1:Sprague-Dawley rats received either saline,probiotics,Escherichia coli,Salmonella enteritidis or Gentamicin via daily gavage for 7 days.Acute liver injurywas induced on the eighth day by intraperitoneal injection of D-galactosamine exceptfor the control group.Samples were collected 24 h later.Bacterial translocation wasevaluated from the liver,sleep,kidney and mesenteric lymph nodes.Liver enzymes,histologic analysis,endotoxin,serum TNF-α,IL-6,IL-10 and IL-12,CD3⁺ and CD4⁺ Tcells in peripheral blood and Peyer's patches,intestinal bacteria,and intestinal mucosalultrastructure were studied.Part 2:Sprague-Dawley rats received either saline,probiotics,Escherichia coli,Salmonella enteritidis,Gentamicin or MgSO₂ via daily gavage for 7 days,GC/MSanalysis the serum metabolic profiles.Results:Part 1:Orally administered probiotics,nonpathogenic E.coli and Gentamicin,respectively,markedly attenuated liver damage,decreased bacterial translocation anddecreased the levels of serum TNF-α,IL-6,IL-10 and IL-12.Treatment with S.enteritidis had opposite results.Only orally supplemented S.enteritidis significantlyaffected the CD3⁺ and CD4⁺ T cells counts in peripheral blood and Peyer's patches.Part 2:Probiotics can markedly reduce the content of Alanine,and in the nonpathogenic E.coli group,it significantly increase in alanine;orally administered S.enteritidis caused many of these amino acids(alanine,leucine,isoleucine,serine)significantly reduce;an overall reduction in gut microflora due to orally administeredGentamicin resulted in a meaningful reduction in proline and butyric acid.Conclusion:We demonstrated that modifications in gut microflora had different effects on theprevention or exacerbation of acute liver injury.Moreover,alterations in gutmicroflora affected liver damage through three major factors:bacterial translocation andthe release of local gut cytokine and endotoxin.The changed gut microflora have diverse effects on the serum metabolicprofiles,especially on the Ammonia.