Analysis Of Altered Gut Microbiota In NAFLD Mouse Models With Different Diets

Objective There are many kinds of diets for the construction of NAFLD mouse model,including high fat diet(HFD)and methionine choline deficient diet(MCDD).Hepatic steatosis and metabolic characteristics induced by these diets vary greatly.For example,HFD can induce insulin resistance and obesity with milder inflammation of liver,while MCDD can induce severer hepatic steatosis and inflammatory reaction without insulin resistance and weight gain.So far gut microbiota alteration of model mice when treated with different diets has not been demonstrated clearly.We attempted to clarify the difference of gut microbes in three types of fatty liver model mice.Methods Twenty six-week-old SPF wild-type C57BL/6 male mice were randomly divided into 4 groups after 7 days' adaptive feeding.They were administrated with different diets and duration: the control group was given normal diet for 12 weeks;HFD group was given high fat diet for 12 weeks;MCDD group was given methionine choline deficient diet for 4 weeks;CD-HFD group was given choline deficient and high fat diet for 12 week.On the last day of modeling,we collected the feces and then performed extraction DNA,PCR amplification,and high throughput sequencing by MiSeq system.Then we analyzed the diversity and species richness of the flora.Finally,liver samples were collected and stained with HE.Results Severest steatohepatitis occurred in the mice fed with MCD diet,followed by the HF diet and the CD-HF diet.There was no significant difference between the MCD group and the control group in the diversity of the bacteria,but the diversity indices of HFD group and CD-HFD group were lower than that of the control group.The MCD diet increased the abundance of Lachnospiraceae,while the HF diet and CD-HF diet increased family S24-7.Conclusions 1.The pathological changes of liver tissues with different dietary NAFLD models were different,and MCD may be more suitable for the construction of NASH model.2.There are differences in the gut microbiota of the NAFLD animal model with different diets,the increase of Lachnospiraceae and S24-7 may be related to the development of NAFLD,but the specific mechanism needs further study.