Alterations in the gut microbiota community are associated with childhood obesity and precocious puberty
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ABSTRACT:
SUBMITTER: Wang L
PROVIDER: S-EPMC11344344 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Precocious puberty mostly stems from endocrine disorders. However, more and more studies show that a high-fat diet (HFD) is closely related to precocious puberty, but its mechanism is unknown. Since gut microbiota is associated with hormone secretion and obesity, it inspires us to detect the mechanism of gut microbiota in triggering precocious puberty. The model of precocious puberty was established by feeding female mice with an HFD from 21 days old. After puberty, the serum hormone levels, gut microbiome sequencing, and metabolomics were collected. DNA was extracted from feces, and the V3-V4 region of the bacterial 16S rRNA gene was amplified, followed by microbial composition analysis. Subsequently, associations between precocious puberty and the microbiota were determined. We found that (1) HFD after weaning caused precocious puberty, increased serum estradiol, leptin, deoxycholic acid (DCA), and gonadotropin-releasing hormone (GnRH) in the hypothalamus; (2) Through correlation analysis, we found that GnRH was positively correlated with Desulfovibrio, Lachnoclostridium, GCA-900066575, Streptococcus, Anaerotruncus, and Bifidobacterium, suggesting that these bacteria may have a role in promoting sexual development. (3) "HFD-microbiota" transplantation promoted the precocious puberty of mice. (4) Estrogen changes the composition and proportion of gut microbiota and promotes precocious puberty. Therefore, the effect of HFD on precocious puberty is regulated by the interaction of gut microbiota and hormones.
| S-EPMC9329965 | biostudies-literature
Project description: Not available
| S-EPMC7842634 | biostudies-literature
Project description:The intestinal microbiota and its derived short-chain fatty acids (SCFAs) can reverse obesity and obesity-related metabolic diseases, but whether it has an effect on obesity complicated by precocious puberty and its potential mechanism need to be further understood. The purpose of this study was to investigate the effect of the gut microbiota and its derived short-chain fatty acids (SCFAs) on obesity-induced precocious puberty rats and their regulatory mechanisms. We constructed obesity-induced precocious puberty rats using a high-fat diet (HFD) had notable similarity to precocious puberty caused by obesity due to overeating in children. We then added acetate, propionate, butyrate or their mixture to the HFD, and investigated the effect of intestinal microbiota and its derived SCFAs on the hypothalamic-pituitary-gonadal axis (HPGA) in rats with obesity-induced precocious puberty. We found that obesity-induced precocious puberty rats had an early first estrous cycle, increased hypothalamic mRNA expression of Kiss1, GPR54 and GnRH, and early gonadal maturation. Meanwhile, the intestinal microbiota imbalance and the main SCFAs production decreased in the colon. The addition of acetate, propionate, butyrate or their mixture to the HFD could significantly reverse the precocious puberty of rats, reduce GnRH release from the hypothalamus and delay the development of the gonadal axis through the Kiss1-GPR54-PKC-ERK1/2 pathway. Our findings suggest that gut microbiota-derived SCFAs are promising therapeutic means for the prevention of obesity-induced precocious puberty and provide new therapeutic strategies with clinical value.
| S-EPMC9782419 | biostudies-literature
Project description:The prevalence of obesity-associated precocious puberty is gradually increasing, but the relationship between gut flora and obesity-associated precocious puberty remains unclear.We analysed the gut flora characteristics of a clinical sample of 30 girls aged 5-8 years using 16s rRNA sequencing. An obesity rat model and a rat model of gut flora transplantation were also constructed. Body weight, body length, abdominal girth, food intake, vulva opening time, and gonadal index were monitored. The secretion levels of estradiol (E2), total cholesterol (TC), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroglobulin (Tg) were analyzed by ELISA. In addition, ovarian and uterine development was observed by HE staining. The mRNA and protein levels of kisspeptin-1 (Kiss-1) and gonadotropin-releasing.We found that the relative abundance of Dialister, Bacteroides, Bifidobacterium, Collinsella, and Romboutsia may be associated with obesity-associated precocious puberty. Obesity promotes gonadal development, and the gut flora of patients with obesity and obesity-associated precocious puberty regulated the gene and protein expression of Kiss-1 and GnRH, promoting precocious puberty and hypothalamic-gonadal axis hormone secretion in rats. In contrast, probiotic intervention slowed gonadal development, reduced hormone secretion, and attenuated hypothalamic-gonadal axis activity. Gut flora promoted obesity-associated precocious puberty by influencing the hypothalamic-gonadal axis, and probiotics have a therapeutic and preventive role in obesity-associated precocious puberty, which may be associated with the Kiss-1/GnRH pathway. These findings may provide some new strategies for clinical treatment and prevention of obesity-associated precocious puberty in girls.
| S-EPMC11582813 | biostudies-literature
Project description:BackgroundCentral precocious puberty (CPP) is characterized by the premature activation of the hypothalamic-pituitary-gonadal axis, resulting in early onset of sexual development. The incidence of CPP has been rising in recent years, with approximately 90% of cases lacking a clearly identifiable etiology. While an association between precocious puberty and gut microbiota has been observed, the precise causal pathways and underlying mechanisms remain poorly understood. The study aims to investigate the potential mechanisms through which gut microbiota imbalances may contribute to CPP.MethodsIn this study, clinical information and fecal samples were collected from 50 CPP patients and 50 healthy control subjects. The fecal samples were analyzed by 16S rDNA sequencing and UPLC-MS/MS metabolic analysis. Spearman correlation analysis was used to identify the relationships between gut microbiota and metabolites.ResultsThe gut microbiota composition in CPP patients was significantly different from that in healthy controls, characterized by an increased abundance of Faecalibacterium and a decreased abundance of Anaerotruncus. Additionally, significant differences were observed in metabolite composition between the CPP and control groups. A total of 51 differentially expressed metabolites were identified, with 32 showing significant upregulation and 19 showing significant downregulation in the CPP group. Furthermore, Spearman correlation analysis indicated that gut microbiota dysbiosis may contribute to altered metabolic patterns in CPP, given its involvement in the regulation of several metabolic pathways, including phenylalanine and tyrosine biosynthesis and metabolism, the citrate cycle (TCA cycle), glyoxylate and dicarboxylate metabolism, and tryptophan metabolism.ConclusionsThe study revealed the gut microbial and metabolite characteristics of CPP patients by integrating microbiome and metabolomics analyses. Moreover, several key metabolic pathways involved in the onset and progression of CPP were identified, which were regulated by gut microbiota. These findings broaden the current understanding of the complex interactions between gut microbial metabolites and CPP, and provide new insights into the pathogenesis and clinical management of CPP.
| S-EPMC11646730 | biostudies-literature
Project description:Idiopathic central precocious puberty (ICPP) is a relatively common condition in preadolescent girls, and its pathogenesis remains to be uncovered. A variety of studies have highlighted the association of gut microbiota (GM) with endocrine diseases, such as obesity, which is commonly associated with ICPP. However, the relationship between GM and ICPP remains unexplored. Feces samples were collected from 25 girls with ICPP (ICPP group) and 23 healthy girls (Control group). We applied 16S rDNA sequencing to compare the GM between two groups. The ICPP group had higher GM diversity and was enriched for several GM species, including Ruminococcus gnavus, Ruminococcus callidus, Ruminococcus bromii, Roseburia inulinivorans, Coprococcus eutactus, Clostridium leptum, and Clostridium lactatifermentans, which are known to be associated with obesity and are related to the production of short-chain fatty acids. Additionally, 36 candidate GM biomarkers for patients with ICPP screening were identified with high accuracy (AUC = 0.95, 95% CI 0.88 to 1). We observed that the GM of the ICPP group was enriched for the microbial functions of cell motility, signal transduction, and environmental adaptation. Positive correlations were also detected between Fusobacterium and follicle-stimulating hormone, and Gemmiger and luteinizing hormone. This study documents relationships between GM and ICPP, and the implication of these findings remains to be determined.
| S-EPMC6987398 | biostudies-literature
Project description:Precocious puberty (PP) is one of the most common endocrine diseases in children, and the pathogenesis is currently unknown. Recent studies on the gut-brain axis have shown that there is a correlation between childhood endocrine diseases and the gut microbiota (GM). To explore the GM characteristics of children with different types of PP, we recruited 27 idiopathic central precocious puberty children (ICPP group), 18 peripheral precocious puberty children (PPP group), and 23 healthy children of the same age (HC group). Their stool samples were subjected to 16S rDNA sequencing. In this study, we found that the OTUs numbers, the annotated genera, and α-diversity of GM of the ICPP and PPP group were all significantly higher than that in the HC group (P < 0.05). The abundance of butyrate-producing bacteria Prevotella, Lachnospiracea incertae sedis, Roseburia, Ruminococcus, and Alistipes was significantly higher in the ICPP group and the PPP group, and Bacteroides and Faecalibacterium showed significantly higher abundance in the HC group. The GM symbiosis network showed that both Bacteroides and Faecalibacterium were negatively correlated with these butyrate-producing bacteria. The abundances of most significantly changed genera were gradually increased from HC to PPP, and to the ICPP group, while only Bacteroides was gradually decreased. After the prediction of the metabolic pathways of the GM, the cell motility, signal transduction, and environmental adaptation were significantly enriched in the ICPP and the PPP groups (P < 0.05), while the carbohydrate metabolism pathway was significantly lower (P < 0.001). Overall, this study showed that the GM composition and predicted functional pattern of children with ICPP and PPP are different from healthy children, and PPP may be a transitional stage between ICPP and HC children, which provide a theoretical basis for clinical intervention based on GM in the treatment of PP.
| S-EPMC9668478 | biostudies-literature
Project description:BackgroundChildhood obesity has important effects on the onset and development of puberty. Although a number of studies have confirmed the relationship between obesity and precocious puberty, little is known about the pleiotropic genes of obesity and precocious puberty and the interaction between genes and environment. There are four objectives: (1) to analyze the incidence of precocious puberty in the general population in China; (2) to verify the direct effect of obesity on children's precocious puberty using a variety of methods; (3) to verify the effect of obesity and its risk gene polymorphism on precocious puberty in a prospective cohort study; and (4) to analyze the interaction effect of genes and environment on pubertal development.MethodsWe will conduct a multi-center prospective cohort study in three cities, which are selected in southern, central, and northern China, respectively. Primary schools in these cities will be selected by a stratified cluster random sampling method. Primary school students from grade 1 to grade 3 (6 to 10 years old) will be selected for the cohort with extensive baseline data collection, including assessment of pubertal development, family demographic information, early development, sleep pattern, dietary pattern, and physical activity. Participants will be followed up for at least three years, and long-term follow-up will depend on future funding.DiscussionThe findings of this multicenter prospective population-based cohort study may expand previous related puberty development research as well as provide important information on the mechanism of early puberty. Targeted interventions can also be developed to improve adolescent health problems related to puberty development based on the available evidence.Trial registrationClinicalTrials.gov Identifier: NCT04113070 , prospectively registered on October 2, 2019.
| S-EPMC9135982 | biostudies-literature
Project description:BackgroundPrevious observational research has demonstrated a possible association between the gut microbiota (GM) and central precocious puberty (CPP). Nevertheless, whether there is a causal relationship between the GM and CPP is uncertain due to the possibility of confounding factors influencing the result.MethodsWe collected summary data from genome-wide association studies of the GM (MiBioGen, n = 18,340) and CPP (FinnGen Consortium, 185 case groups and 395,289 controls). Most of the participants were of European origin. Mendelian randomization analysis was utilized to investigate the causal relationship between the GM and CPP using the inverse-variance weighted average technique, the weighted median, and Mendelian randomization Egger. The reliability of the results was evaluated using the leave-one-out test and sensitivity analyses, including heterogeneity and horizontal pleiotropy testing.ResultsAccording to the inverse-variance weighted average technique, there was a substantial correlation between CPP and the composition of the GM. Specifically, the relative abundance of the genus Bacteroides (OR 0.222, 95% CI 0.06-0.822, P = 0.024) and Alistipes (OR 0.197, 95% CI 0.056-0.697, P = 0.012), and others, showed significant associations. Furthermore, associations with the phylum Euryarchaeota, the orders Gastranaerophilales, and Rhodospirillales, the families Bacteroidaceae, and Desulfovibrionaceae were also observed. Sensitivity analyses and the leave-one-out test generated positive results for the genus Alistipes, implying that this genus is reliable and reduces the risk of CPP.ConclusionsThe composition of the GM may have a causal effect on CPP. The present finding that Alistipes may be protective against CPP is expected to offer novel insights into the management of CPP.
| S-EPMC11609932 | biostudies-literature
Project description:PURPOSE:Single-nucleotide polymorphism (SNP) markers within LIN28B have been reported to be related to the timing of pubertal growth. However, no study has investigated the frequency of genetic markers in girls with precocious puberty (PP) or early puberty (EP). This study aimed to determine the frequency of putative genetic markers in girls with PP or EP. METHODS:Genomic DNAs were obtained from 77 and 109 girls that fulfilled the criteria for PP and EP, respectively. The controls in this study were 144 healthy volunteers between 20 and 30 years of age. The haplotypes were reconstructed using 11 SNPs of LIN28B, and haplotype association analysis was performed. The haplotype frequencies were compared. Differences in the clinical and laboratory parameters were analyzed according to the haplotype dosage. RESULTS:Eleven SNPs in LIN28B were all located in a block that was in linkage disequilibrium. The haplotype could be reconstructed using 2 representative SNPs, rs4946651 and rs369065. The AC haplotype was less frequently observed in the PP group than in the controls (0.069 vs. 0.144, P=0.010). The trend that girls with non-AC haplotypes tended to have earlier puberty onset (P=0.037) was illustrated even in the EP+PP patient group by Kaplan-Meier analysis. CONCLUSION:The results of the present study showed that non-AC haplotypes of LIN28B had a significant association with PP in girls.
| S-EPMC3488615 | biostudies-literature