Protective Effect Of Fecal Microbiota Transplantation (FMT) On D-galactosamine-induced Acute Liver Failure In Mice Based On Gut Microbiota

Objective: To investigate the protective effect of fecal microbiota transplantation(FMT)on the liver of mice with D-aminogalactose-induced acute liver failure(ALF),and to preliminarily investigate its mechanism of action.Methods: 1.85 male BALB/c mice were randomly divided into 6 groups: a group of10 mice for normal control group(CON group): fed with standard chow without special treatment;b group of 15 mice for model group(D-G group): fed normally after 2 weeks of normal feeding followed by intraperitoneal injection of D-aminogalactose without special treatment;c group of 15 mice for FMT treatment for 3 days(FMT-treated3 d group):D-aminogalactose was injected intraperitoneally after 2 weeks of normal feeding,and immediately after the injection,FMT gavage(200ul/each)was given for 3 days;group d is FMT-pre14 d group: FMT gavage(200u/each)was given for 2 weeks during feeding,and D-aminogalactose was injected intraperitoneally immediately after the gavage.Group e:FMT-pre7 d group(15 animals): FMT bacteria were gavaged for 1 week(200ul/animal)and D-amino galactose was injected intraperitoneally immediately after gavage;Group f:FMT-pre3 d group(15 animals): FMT bacteria were gavaged for 3 days(200ul/animal)and D-amino galactose was injected intraperitoneally immediately after gavage.D-amino galactose was injected intraperitoneally immediately after gavage.The feces of each group of mice were collected before and after the injection of D-aminogalactose and before and after the intervention of FMT,and the fecal DNA was extracted by the Fecal Genome Kit for 16 S r RNA sequencing.3.The serum and liver and spleen tissues of each group of mice were collected for subsequent analysis.4.The therapeutic effect of FMT on acute liver failure in mice.Results: 1.Compared with the mice in the normal control group(CON group),the mice in the D-G group showed symptoms such as acute liver injury and were successfully modeled;2.The survival rate of mice in the D-G group was significantly lower than that in the FMT prevention group and the FMT treatment group;3.The body weight and liver weight of mice in the FMT-pre14 d group,the FMT-pre7 d group and the FMT-treat3 d group were significantly increased compared with those in the D-G group(p<0.05);4.Histopathological damage to the liver of mice in the FMT-pre14 d,FMT-pre7 d and FMT-treat3 d groups was less severe than that in the D-G group;5.The expression of the inflammatory factor IL-10 in the serum of mice in the FMT-pre14 d,FMT-pre7 d and FMT-treat3 d groups was significantly higher than that in the D-G group(p <0.05),while the expression of pro-inflammatory factors IL-6 and LBP was decreased compared with the D-G group(p<0.05);6.The gut microbiota diversity of mice in the FMT-pre14 d,FMT-pre7 d and FMT-treat3 d groups was increased compared with the D-G group,and the abundance of probiotic bacteria was significantly increased.Conclusion: FMT can effectively alleviate the acute liver failure induced by D-aminogalactose in mice,and its mechanism of action may be that FMT inhibits the development of acute liver failure by regulating the structure of intestinal flora and activating the IL-10 pathway.