The Diferences Of Gut Microbiota In Obesity And Obesity Resistance Mice Fed With High Fat Diet

Background: High fat and high energy diet is the most important risk factor causing overweight and obesity.However diet-induced obesity resistance has been observed both among human and other animal species.The underlying physiological mechanism remains unclear.Gut microbiota plays an important role in the development of wide ranges of metabolic disorders,including aggravating obesity,type-2 diabetes and cardiovascular diseases.So far,however,there has been few discussions about the possible roles of gut microbiota regulating metabolism that causing obesity or obesity resistance under high-fat diet(HFD)feeding.In this study,C57BL/6J mice in control group were fed with low-fat diet(LFD).Other animals fed with high fat diet were divided into diet-induced obesity(DIO)group or diet-induced obesity resistance(DIR)group according to their body weight gain compared with LFD group.Another group of C57BL/6J mice were randomly assigned to three subgroups,which received fecal microbiota transplantation(FMT)prepared from LFD,DIO and DIR mice respectively,and then fed with HFD.Body weight gain,metaboliccharacteristics were observed in FMT recipient mice to determine exactly how the difference of gut microbiota affects diet-induced obesity or diet-induced obesity resistance.Methods: Six-week-old C57BL/6J mice were randomly assigned to LFD and HFD.After 10 weeks,the mice in HFD group were divided into DIR or DIO according to their body weight gain.Mice with body weights lower than that of LFD group((?) + 3SD)were allocated to DIR.The rest were set as DIO.After 12 weeks feeding,body weight analysis,glucose tolerance test was carried out to determine the metabolic characteristics of the three groups.After the donor mice were executed,extracted the bacterial DNA from the cecum content,and the intestinal microbial diversity was analyzed by Miseq sequencing.Sex-week-old C57BL/6J mice were selected as fecal microbiota transplant recipients.One week after transplantation,all recipient mice were fed HFD for 12 weeks.Body weight changes were observed,and the energy metabolism were measured by indirect calorimetry.Result: The partial least squares-discriminant analysis(PLS-DA)showed that the gut microbiota composition were different among three donor groups.There were 5 OTUs at the specie level which were significantly different among three donor groups(results showed the top 15 abundance of microbiota).The Bacteroides thetaiotaomicron abundance in DIR mice was significantly lower than that of DIO mice.The expressionlevel of FIAF in small intestinal mucosa of DIO mice was lower than that in LFD group,and the expression level of GPR43 in small intestinal mucosa of DIO mice was higher than that in DIR group.Among the recipient mice fed with HFD for 6 weeks,the weight gain was significantly lower in the mice receiving FMT prepared from DIR,compared with those receiving FMT from DIO.However,the oxygen consumption,carbon dioxide production and body temperature were slightly higher than those of their counterpart.Conclusions: This study has shown that gut microbiota community changes,especially lower abundance of Anaerotruncus may contribute to HFD-induced obesity resistance.Further research regarding the role of gut microbiota in regulating the nutrients absorption,energy metabolism,would be of great help in obesity prevention and treatment.