| Objective: This study aims to establish a rat model of alcoholic liver injury and explore the "gut-liver" axis mechanism of the protective effects of different doses of yeast extract on alcoholic liver injury.So as to provide a theoretical basis for the subsequent research and development of functional products for the prevention of alcoholic liver injury.Methods: A total of 77 Wistar rats were randomly divided into the following groups:blank control group(CK),yeast extract group(YE),liquid diet control group(LC),alcohol modeling group(AL),low-dose yeast extract intervention group(YEL),highdose yeast extract intervention group(YEH),and silymarin intervention group(PC).Rats in the CK and YE groups were given regular maintenance feed,while rats in the LC group were given Tipoe-Nanji liquid control diet.The remaining groups were all given Tipoe-Nanji alcoholic liquid diet.The experiment lasted for 8 weeks.After gavage,rat liver samples were collected for biochemical indicators detection,and liver pathological sections were prepared.At the same time,fresh fecal samples were collected,and the diversity of rat intestinal flora was analyzed using 16 s r RNA gene sequencing technology.In addition,differences in metabolites among the groups were detected by combining widely targeted metabolomics and untargeted metabolomics technology.Results:(1)According to various indicators such as liver function,oxidative stress and inflammatory response,combined with the results of liver tissue histopathological,it has been proven that high-dose yeast extract does not cause damage to rat liver tissue,and could enhance the liver’s antioxidant capacity and anti-inflammatory abilities.(2)Compared with the alcohol modeling group,in the high-dose yeast extract intervention group,the liver index and the levels of aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase,lactate dehydrogenase,triglyceride and total cholesterol all decreased and the level of alcohol dehydrogenase increased,with statistically significant differences(P<0.05);The liver oxidative stress indicators showed that the levels of glutathione peroxidase,superoxide dismutase,total antioxidant capacity and hydroxyl radical scavenging ability in the two yeast extract intervention groups,as well as the silymarin intervention group all increased,while the MDA decreased,with statistically significant differences(P<0.05).Liver inflammation indicators showed that the levels of inflammatory cytokines including interleukin-1β,tumor necrosis factor-α,interferon-γ,total nitric oxide synthase and inducible nitric oxide synthase in the high-dose yeast extract intervention group all decreased,with statistically significant differences(P<0.05).(3)The results of 16 s r RNA gene sequencing revealed that the β-diversity of intestinal flora in the high and low-dose yeast extract intervention groups,as well as the silymarin intervention group was higher than that in the alcohol modeling group(P<0.05);Compared with the AL group,the intervention of low-dose yeast extract could reduce the relative abundance of Ruminococcus Peptococcus and Faecalibacterium in the intestinal flora(P<0.05);the intervention of high-dose yeast extract reduced the relative abundance of Helicobacter,Romboutsia and Faecalibacterium(P<0.05).(4)Peptococcus showed a significant positive correlation with ALT,AST,AKP and MDA,and a significant negative correlation with ADH,SOD,GSH and T.AOC.Faecalibacterium demonstrated a significant positive correlation with MDA and TC,and a significant negative correlation with SOD.Ruminococcus exhibited a significant positive correlation with ALT,AST,AKP,TC,TG,and MDA,and a significant negative correlation with ADH,SOD,GPX,and OH scavenging ability.Romboutsia was significantly positively correlated with TNOS and i NOS,while Faecalibaculum had a significant positive correlation with TC and i NOS,but a significant negative correlation with GPX.(5)Metabolomics analysis revealed that metabolites such as 2-aminoethanesulfonic acid,trigonelline,and 3-indoleacrylic acid were significantly up-regulated in the low-dose yeast extract intervention group,while acetylcholine,L-methionine and 12-hydroxyjasmonic acid were significantly upregulated in the high-does yeast extract intervention group.In contrast,metabolites such as histamine,adenosine,5’-adenine nucleotide,2-methylhippuric acid,and phenylacetylglycine were significantly downregulated.All of the above regulation trends can promote health to varying degrees.Conclusions:(1)Yeast extract has no negative effects on the liver tissue of healthy rats,and can improve the antioxidant and anti-inflammatory capabilities,making it suitable for intervention research on alcoholic liver injury in rats.(2)Both high and low-doses yeast extracts can exert varying degrees of protective effects on liver injury in alcoholic liver injury in rats and improve intestinal flora dysbiosis.(3)The intervention effects of high-dose yeast extract on oxidative stress,inflammatory response and metabolic regulation are superior to those of low-dose yeast extract. |
