Regulation Of Body Weight Gain In Mice By Bacillus Subtilis J-15 And Its Metabolites

The epidemic of obesity and its associated diseases such as diabetes and metabolic syndrome seriously threaten people’s life and health,and the prevention and treatment of obesity has become increasingly important.Some studies have found that probiotics and their metabolites can improve glucolipid metabolism to treat obesity by modulating intestinal flora.In the previous study,the metabolites of Bacillus subtilis J-15 were found to reduce body weight gain and improve immunity in mice,which has the potential value of obesity prevention.In this study,on the basis of the previous study,the effect of Bacillus subtilis metabolite n-butanol part extract,Bacillus subtilis J-15 and its metabolite main component antimycobacteriocin were investigated by gavage in mice to study the effect of J-15 bacteriophage and its metabolite on body weight gain of mice,and its effect on intestinal flora.Finally,the therapeutic effects of J-15 bacteriophage and its metabolites on weight gain in obese mice were investigated by establishing an obesity model in mice.To lay the foundation for the development of using Bacillus subtilis J-15 and its metabolites in the application of treating obesity.The results of the present study are as follows.（1）Gavage treatment of mice with Bacillus subtilis J-15 metabolite n-butyl alcohol extract（90 mg/kg）for 30 days had no significant effect on body weight on days 10-11 and significantly inhibited their body weight gain from days 12-30（P<0.05）;gavage treatment for 30 days significantly increased the abundance of intestinal flora in mice,and the ratio of Bacillus phylum to Bacillus phylum was up-regulated;significantly reduced The TG,LDL and epididymal fat content of the liver were significantly reduced.（2）Mice treated with Bacillus subtilis bacterial suspension（2×10~9CFU/ml）at a dose of 1 time/1 day by gavage,and the rate of body weight gain was significantly lower（P<0.05）after stopping treatment after 1 or 14 days of gavage;the liver TG,HDL,LDL and epididymal fat content of mice in both groups were significantly lower than the control;and the structural changes of intestinal flora compared to the control group were consistent with the The changes in the structure of intestinal flora compared with the control group were consistent with the changes in the metabolite acetone extract treatment of the bacterium.This suggests that Bacillus subtilis J-15may regulate the body weight gain of animals by affecting their intestinal bacteria.After stopping the gavage of Bacillus subtilis J-15 by real-time fluorescence quantification,the amount of this strain in the small intestine of mice gradually decreased and was basically undetectable by 45 days,indicating that Bacillus subtilis J-15 could not colonize the intestine of mice for a long time.（3）The effect of this substance on body weight,intestinal bacterial structure and mouse liver TG,HDL,LDL was found to be similar to that of n-butanol extract and bacteriophage treatment,indicating that antimycobacteriocin may be the key substance of Bacillus subtilis J-15 in regulating body weight in mice.（4）The obese mice model was constructed and treated with J-15 bacteriophage,metabolite n-butanol extract and antimycobacteriocin by gavage,which significantly reduced the body weight of the mice,and significantly decreased the plasma levels of TC,HDL and LDL,and significantly increased the expression of HSL and ATGL,the genes encoding lipid degradation phase regulating enzymes;SREBP-1,the gene encoding lipid synthesis-related enzymes,was significantly reduced.SREBP-1,fatty acid synthase and acetyl coenzyme A carboxylase were significantly reduced at the protein level,but no significant changes were observed for triglyceride lipase and deacetylase.The combined analysis of the effects of J-15 bacteriophage,n-butanol extract and antimycobacteriocin on body weight gain and intestinal flora of mice showed that all three of them reduced the rate of body weight gain and had therapeutic effects on obesity in mice by affecting the structure of flora in the small intestine of high mice,especially by reducing the abundance of thick-walled bacteria phylum and increasing the abundance of Bacillus phylum,or by regulating the expression of lipid metabolism-related enzymes.This provides an experimental basis for the development of Bacillus subtilis J-15 and its metabolites for obesity prevention and treatment.