Study On The Effect Of Butylparaben On Gut Microbiota And Liver Glycometabolism Of Male Rats

Parabens mainly include methyl-paraben,ethyl-paraben,propyl-paraben and butyl-paraben,etc.,which are widely used as preservative and one type of endocrine disruptors(EDC).People exposure to parabens through diet,breathing or smearing,etc..In recent years,it is found that many EDC are also called metabolism disrupting chemical(MDC).The composition of gut microbiota and lipopolysaccharide(LPS),which is one of the mainly metabolites of gut microbiota,are closely related to the infalmmatory response and metabolic syndrome.As parabens belonging to endocrine disruptors and widely used as preservatives,parabens may affect the function of metabolic and change the stucture and function of gut microbiota.In our study,we chose butyl-parabens(n-BP)as the objectives of the study material,high fat diet as a positive control.Rats were randomly divided into five groups:blank control group,solvent control group,BP group(n-BP 160mg/kg/d+high fat diet),BP+HFD group(n-BP 160mg/kg/d+high fat diet),HFD group(high fat diet).The exposured period were 8 weeks by gavaging.The study was to investigate the effect of n-BP on the composition of gut microbiota and the effect on glycometabolism though the change of gut microbiota and LPS.1.The effect of n-BP on the function of rats' metabolism1)The effect of n-BP on body weight,organ and metabiolismWe chosed the weight of body and organ,oragn coefficient,insulin resistance index,blood pressure and blood lipid as terminal point.At the forth week,there was no significant difference in weight of groups(P>0.05);both liver coefficient and epididymal fat coefficient of BP+HFD group and HFD group were higher than blank control group(P<0.05).At the eighth week,the weight,liver coefficient,epididymal fat coefficient and perirenal fat of BP group and BP+HFD group were higher than the blank control group(P<0.05).2)The effect of n-BP on glycometabolism and lipid metabolismWe used biochemical machine to analyze serum lipid,glucometer and blood pressure to analyze rat fasting glucose and blood pressure,and Radioimmunoassay kit to detect insulin levels.Exposed to n-BP alone had no significant effect on IR,blood pressure or blood lipid levels(P>0.05).n-BP had no significant effect on liver or pancreas.2.The effect of n-BP on male rats' gut microbiota1)The effect of n-BP on the structure of gut microbiotaUsing 16S rRNA to analyze the structure and the abundance and diversity,as well as the compositons of gut microbiota.Both n-BP and high fat diet would change the structure of gut microbiota,resulting in the reduction of bacteria abundance and diversity(P<0.05);high fat diet led to the increase of abundance of Fimicutes and reduction of Bacteroidetes(P<0.05),while n-BP had no effect on Fimicutes or Bacteroidetes(P>0.05).Exposed to n-BP could significantly increase the proportion of gram negative bacteria of the dominant bacteria at genus level(P<0.05).2)The effect of n-BP on serum LPSWe used Radioimmunoassay kit to detect serum LPS,RT-PCR and westernblot to test the expression of TLR-4 in liver and ileum.Exposed to n-BP and high fat diet can increase LPS(P<0.05),and there was no significant difference between these two factors.When combined with high fat diet,n-BP could induce the level of LPS and the expression of TLR-4 in ileum higher(P<0.05).3.The effect of n-BP on liver glycometabolism1)The effect of n-BP on serum inflammatory cytokinesWe used Radioimmunoassay kit to detect serum inflammatory cytokines.Both n-BP and high fat diet can increase serum TNF-? through increasing LPS,resulting in the inflammatory response(P<0.05).High fat diet can also increase IL-10(P<0.05),which is one of anti-infammatory cytokines.While exposed to n-BP alone had no effect on IL-10(P>0.05).2)The effect of n-BP on the expression of GLUT-2 and INSR of liverWe used RT-PCR and westernblot to test the expression of GLUT-2 and INSR of liver.Rats exposed to n-BP had lower expression of GLUT-2 of liver(P<0.05),which might impair the function of glucose metabolism.High fat die can descrease the expression of INSR of liver(P<0.05),while exposed to n-BP alone had no effect on the expression of INSR of liver.4.Conclusion1)Exposed to n-BP can reduce the abundance and diversity of gut microbiota of rats,change the structure of gut microbiota,increase the abundance of gram negative bacteria of the dominant bacteria at genus level,as well as increase the level of the metabolite of gut microbiota of LPS.2)n-BP can increase TNF-a and reduce the expression of GLUT-2 of liver through altering the structure of gut microbiota.GLUT-2 might be one of biomakers of liver glycometabolism effected by n-BP.