Research Of Gut Microbiota Composition And Obesity Propensity In Mice

Gut microbiota playsan important role in energy harvest, altering adipose metabolism and inflammation in host. It is sensible that gut microbiota is closely related to the development of obesity andmetabolic syndrome. High fat diet will induce obesity-resistance(DIO-R)and obesity-prone(DIO-P) two different phenotypes. It is meaningful for understanding obesity mechanism to explore the relationship betweengut microbiota anddifferent obesity phenotypes.C57BL/6 mice were randomly divided into normal chow group(NC) and high-fat group for the feeding. After obesity phenotype appearing differentiation, high-fat group can be divided into DIO-R and DIO-P. Terminal restriction fragment polymorphism(T-RFLP) and real-time PCR(RT-PCR) were used to analysis the gut microbiota characteristics at initial time and after 7, 17, 27 weeks of intervention in mice. Short chain fatty acids(SCFAs) were tested at the same time. Executed mice at 3 time points, we analyzed the concentration of blood endotoxin(LPS) and inflammatory cytokines in plasma, the expression of TLR4、GPR41、Fiaf、Zo-1、Occludin and Muc2 in the ileum.It was found that high-fat diet induced two different phenotype of obesity.Body weight of DIO-P was significantly higher than the NC group and DIO-R group(P<0.05), and DIO-R group was closed to NC in early, but gradually higher than NC in later period(P<0.05); Diversity and stability of gut microbiota in DIO-P group were drived to lower levels. The content of Lactobacillus, Bifidobacterium, Akkermansa muciniphila were significantly decreased while increasing Staphylococcus aureus, Enterobacter cloacae in DIO-P group. The DIO-R mice were unaffected at early stage, but in the later period, they gradually inclined to obesity characteristics. Gut microbiota of different obesity phenotype mice were significant different at start moment.Content of acetate, butyrate significantly reduced while propionic acid increasing in HFD groups. There are differences between DIO-R and DIO-P in early period. Endotoxin content got a significant rise in HFD groups, but DIO-R was significantly lower than DIO-P on 7 and 17 weeks(P<0.05). The expressions of TLR4(receptor of LPS) and GPR41(receptor of SCFAs)were significantly higher in DIO-P, making inflammation signal transmitted from lumen to the body. Fiaf can strengthen the body adipose decompose, inhibit fat synthesis. Fiaf m RNA in DIO-P group was significantly lower than DIO-R group(P<0.05). Zo-1, Occludin, and Muc2 are important components of the intestinal mucosa barrier. Their expressions were significantly lower in DIO-P, suggesting the damage of intestinal barrier. Finally, we found that DIO-P promoted a marked increasing in the level of inflammatory cytokines, and decreasing anti-inflammatory cytokine, appearingsystemic chronic inflammation.In conclusion, this study shows that gut microbiota isthe key influent factor in the development of DIO-R and DIO-P.Gut microbiota may induce obesity through damaging the intestinal mucosal barrier, inducing inflammation and disrupting the adipose metabolism.