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Link to original content: http://pubmed.ncbi.nlm.nih.gov/39572735/
Gut flora influences the hypothalamic-gonadal axis to regulate the pathogenesis of obesity-associated precocious puberty - PubMed Skip to main page content
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. 2024 Nov 21;14(1):28844.
doi: 10.1038/s41598-024-80140-8.

Gut flora influences the hypothalamic-gonadal axis to regulate the pathogenesis of obesity-associated precocious puberty

Ying Qian  1 , Xiaodan Fang  1 , Yan Chen  1 , Mingxing Ding  2 , Min Gong  3
Affiliations

Gut flora influences the hypothalamic-gonadal axis to regulate the pathogenesis of obesity-associated precocious puberty

Ying Qian et al. Sci Rep. .

Abstract

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.

Keywords: Children; Gut flora; Obesity; Precocious puberty.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethical approval: Study approval statement: This study protocol was reviewed and approved by the Ethics Committee of Jinhua People’s Hospital (No. IBR-20220009-R). Human or animal rights: All participants were informed about the study and signed an informed consent form, and the study was approved by the Ethics Committee of Jinhua People’s Hospital (No. IBR-20220009-R). Consent for publication: The authors declared that all participants consented to the publication of this study.

Figures

Fig. 1
Fig. 1
Abundance of top 30 gut flora stacked bar chart (A total of 30 samples, 10 in each group).
Fig. 2
Fig. 2
Characteristics of intestinal flora among different populations. (A): Ratio of Baceteroidetes/Firmicutes. (B): Abundance of top 30 gut flora heat map analysis (A total of 30 samples, 10 in each group). (C): Serum leptin levels were examined by Elsa. (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.001 vs. normal group; Results were analyzed by one-way ANOVA)
Fig. 3
Fig. 3
General condition monitoring in obesity model rats. (A): Rats were tested for body length every two weeks. (B): Rats were tested for abdominal girth every two weeks (C): Rats were tested for body weight every two weeks. (D): Vulva opening time. (E), (F): Uterus and ovaries index. (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.001 vs. normal group; Results were analyzed by one-way ANOVA).
Fig. 4
Fig. 4
Hypothalamic-gonadal axis function tests. (A)–(E): Secretion levels of Tg (A), TC (B), LH (C), FSH (D), and E2 (E). (F), (G): The mRNA levels of Kiss-1 and Gn-RH were examined by q-pcr. (H): The protein levels of Kiss-1 and Gn-RH were examined by Western blotting (Gels/blots were cut from different parts and exposed, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.001 vs. normal group; Results were analyzed by one-way ANOVA).
Fig. 5
Fig. 5
HE staining assessed ovarian and uterine development. (A): The development of the ovary was observed by HE staining. (B): Uterine development observed by HE staining.
Fig. 6
Fig. 6
General conditions and hormone secretion levels in patient gut flora transplanted rats. (A)–(D): Monitoring of abdominal circumference (A), body weight (B), food intake (C) and body length (D) in rats. (E)–(I): Secretion levels of Tg(E), TC(H), LH(G), FSH(G), and E2(I). J-K: The mRNA levels of Kiss-1 and Gn-RH were examined by using q-pcr. (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.001 vs. normal group; Results were analyzed by one-way ANOVA).
Fig. 7
Fig. 7
Hypothalamic protein levels and HE staining of the uterus and ovaries. (A): The protein levels of Kiss-1 and Gn-RH were examined by using Western blotting. (B): The development of the ovary was observed by HE staining. (C): Uterine development observed by HE staining. (Gels/blots were cut from different parts and exposed, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.001 vs. normal group; Results were analyzed by one-way ANOVA).
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