The Association of Gut Microbiota With Idiopathic Central Precocious Puberty in Girls

Abstract

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.

Keywords: 16S rDNA sequencing; gut microbota; idiopathic central precocious puberty; leptin; short chain fatty acids.

Figure 1

Flowchart illustrating the inclusion/exclusion of individuals in the study.

Figure 2

Non-metric multidimensional scaling (NMDS) distribution and microbiota diversity in ICPP and Control group. (A) NMDS analysis, the samples from ICPP group was clustered together, and they are separated from those of the Control group. (B) The diversity in the bacteria community was significant lower in the Control group than that in the Case group (P < 0.01). (C) The Chao indexed of gut microbiota was obviously lower in Control group than that in ICPP group (P < 0.01).

Figure 3

The discrepant genera and species between ICPP and Control group. Thirteen distinct genera and 16 discrepant bacterial species were found between ICPP and Control group. Most of them enriched in ICPP group. The asterisks stand for the p < 0.05.

Figure 4

Gut microbiota (GM) biomarkers for classifying ICPP patients from healthy girls. (A) Mean Decrease Accuracy and Mean Decrease Gini of attributes as assigned by the random forest. (B) The accuracy of candidate GM biomarkers was verified with cross-validation. The AUC value was calculated and receiver operating characteristic curves (ROC) were drawn with five repeats.

Figure 5

Relative abundance (log10 transformation) heat map of distinct KEGG categories in the ICPP and Control groups. Based on the functional classifications of the KEGG database, the functional categories between two groups were compared. FDR values indicated by asterisks on the right of Figure (***FDR < 0.001, **FDR < 0.01, *FDR < 0.05). The enrichment of functional category is indicated by cross.