Objectivs1.The structural characteristics of the intestinal flora and the content characteristics of short chain fatty acids(SCFAs)of children with Central Precocious Puberty(CPP)were analyzed.2.The estradiol(E2),luteinizing hormone(LH),follicle stimulating hormone(FSH),prolactin(PRL),testosterone(T),progesterone(P)and other sex hormone levels,bone age,ovarian and uterine ultrasound examination in children with CPP were detected.The information on the height,weight and eating habits of precocious children,obese children and normal healthy children were collected.And the correlation between these clinical indicators,dietary characteristics and the structure of the intestinal flora and SCFAs levels of each group of children were analyzed.3.The role of the intestinal flora in the development of children with CPP was explored,and the relationship between CPP and obesity in children was analyzed.By analyzing and adjusting the structure of intestinal flora in children with CPP,the aim is to find a way to prevent and delay the occurrence of CPP.MethodsThe children with CPP were patients treated at The affiliated hospital of Jiangsu University and Subei People’s hospital from September 2018 to October 2019.They were divided into pre-treatment group and post-treatment group.At the same period,the simple obese children and normal body mass index(BMI)children who were examined in the hospital were selected as obese group and the control group respectively.When the children with CPP were admitted to the hospital,accoding to the clinical pathways,the pre-treatment group completed the Gonadotropin releasing hormone(Gn RH)stimulation test according to the clinical path,the pre-treatment group and post-treatment group also should complete the indicators of E2,FSH,LH and other sex hormone levels,and the examinations of bone age,craniocerebral and pituitary magnetic resonance,ovarian and uterine ultrasound.Fresh stool samples from children in CPP group,obesity group and normal healthy group were collected.16 s r RNA sequencing and gas chromatography was used to analyze the structural characteristics of intestinal flora and the levels of it’s metabolites SCFAs in stool samples.The correlation was analyzed between bone age,BMI,duration of treatment with triptorelin,levels of sex hormones such as E2 and FSH,uterus and ovarian volume with intestinal flora and its metabolite SCFAs in precocious children.Questionnaires were used to investigate and analyze the diets structure of the children in each group.Results1.The Ace index and Chao1 index,which represent the abundance of intestinal flora at pre-treated CPP group were reduced obviously compared with the control group(both P < 0.05),but there had no significant difference compared with that of the obesity group(P>0.05).Although the Ace index and Chao1 index at the post-treated CPP group were higher than that of the obesity group(both P>0.05),these two indexes had no significant difference when compared with the obesity group(P>0.05).The Shannon index and Simpson index representing the diversity of intestinal flora had no significant difference in each group(P>0.05).2.The phylum level of intestinal flora in each group showed that the abundance of Bacteroides in the CPP pre-treatment group,post-treatment group and obesity group was higher than that of the control group(P<0.05),while the abundance of Firmicutes and Actinomycetes was significantly reduced(P<0.05);Compared with the normal group,the abundance of Verrucobacterium was significantly decreased at the pre-treatment group and post-treatment group,while the abundance of Verrucomicrobia in the post-treatment group was significantly higher than pre-treatment group(P<0.05);There was no significant difference in the abundance of Bacteroides phylum,Firmicutes phylum and Actinomycetes phylum in the pre-treatment group compared with the obesity group(P > 0.05),and the abundance of the Proteobacteria had no significant difference in each group(P>0.05).3.The genus levels of intestinal flora in each group of children showed that the abundance of Bacteroides,Prevotella,Mycobacterium and Parabacteroides in the pre-treatment group was increased obviously while compared with the control group(P<0.05),and the abundance of Lactobacillus,Bifidobacterium,Lacetospirillum,and Blauterella decreased significantly(P<0.05).The abundance of Paraprevotella at pre-treatment group was increased obviously while compared with the post-treatment group(P < 0.05),the abundance of Blautia was significantly lower(P<0.05);There was no significant difference in the changes of the abundance of Bacteroides,Lachnospiraceae,Faecalibacterium,Bifidobacterium,Blautia,Parabacteroides,Ruminococcus,Alistipes,Prevotella and Lactobacillus in the pre-treatment group compared with the obesity group(P>0.05).4.Principal component analysis(PCA)showed that the structure of the intestinal flora in the pre-treatment CPP group was significantly different fromf the control group.5.The results of SCFAs of intestinal flora metabolites by quantitative detection in children of each group showed that total SCFAs in the pre-treatment group was significantly higher than those in the control group(P<0.05),while the content of acetic acid,isobutyric acid,and butyric acid were significantly lower than those of the control group(P<0.05);The content of acetic acid,isobutyric acid,butyric acid and total SCFAs had no significant difference among pre-treatment group,post-treatment group and obesity group(P>0.05).6.In children with CPP,the treatment time,bone age,sex hormone level,the volume of ovaries and uterine were related to richness of bacteria such as Bifidobacterium and Lactobacillus separately,and also related to the acetic acid,propionic acid and butyric acid in unit mass of feces.7.The probability of eating off-season fruits in the CPP group was significantly higher than that of the obesity group and the control group(P < 0.05).The probability of eating meat,taking nourishing foods and beverages in CPP group and the obesity group was significantly higher than that of the control group(P < 0.05).There was no significant difference for eating habits between those two groups(P>0.05).Conclusions1.The abundance of the intestinal flora in children with CPP had decreased significantly,and the phylum level and genus level structure of the intestinal flora had changed,and the richness level of some bacteria was related to the level of sex hormones.It is suggested that the disorder of the intestinal flora may be the potential factors caused CPP in children.2.There was a significant difference in the level of SCFAs such as Acetic acid between children with CPP and normal children.The structural disorder of the intestinal flora may result in the change of SCFAs,thereby affecting the metabolism of substance and energy in children with CPP,and may further promote the occurrence of CPP in children.3.There was a certain similarity between the structure of intestinal flora and the SCFAs of metabolites in children with the CPP group and the obesity group,which added new evidence for exploring the potential mechanism of CPP and obesity. |