Gut microbiome combined with metabolomics reveals biomarkers and pathways in central precocious puberty

Abstract

Background Central precocious puberty (CPP) is a common disease in prepubertal children and results mainly from disorders in the endocrine system. Emerging evidence has highlighted the involvement of gut microbes in hormone secretion, but their roles and downstream metabolic pathways in CPP remain unknown. Methods To explore the gut microbes and metabolism alterations in CPP, we performed the 16S rRNA sequencing and untargeted metabolomics profiling for 91 CPP patients and 59 healthy controls. Bioinformatics and statistical analyses, including the comparisons of alpha and beta diversity, abundances of microbes, were undertaken on the 16S rRNA gene sequences and metabolism profiling. Classifiers were constructed based on the microorganisms and metabolites. Functional and pathway enrichment analyses were performed for identification of the altered microorganisms and metabolites in CPP. Results We integrated a multi-omics approach to investigate the alterations and functional characteristics of gut microbes and metabolites in CPP patients. The fecal microbiome profiles and fecal and blood metabolite profiles for 91 CPP patients and 59 healthy controls were generated and compared. We identified the altered microorganisms and metabolites during the development of CPP and constructed a machine learning-based classifier for distinguishing CPP. The Area Under Curves (AUCs) of the classifies were ranged from 0.832 to 1.00. In addition, functional analysis of the gut microbiota revealed that the nitric oxide synthesis was closely associated with the progression of CPP. Finally, we investigated the metabolic potential of gut microbes and discovered the genus Streptococcus could be a candidate molecular marker for CPP treatment. Conclusions Overall, we utilized multi-omics data from microorganisms and metabolites to build a classifier for discriminating CPP patients from the common populations and recognized potential therapeutic molecular markers for CPP through comprehensive analyses.

Multi-omic analysis of precocious puberty girls: pathway changes and metabolite validation

“…Li et al performed analysis of proteomics and metabolomics in girls with CPP and found some key differential proteins and metabolites, including MMP9, SPP1, CDC42, POSTN, COL1A1, BMP1, and phosphocholine (16:1(9Z)/16:1(9Z)) (18). Huang et al performed 16S ribosomal RNA (rRNA) sequencing and untargeted metabolomic profiling of CPP patients; it was revealed that nitric oxide synthesis and Streptococcus were closely associated with CPP (19). Different from these studies, in this study, we conducted metabolomic analysis of fecal samples of clinical PP girls and animal models and further validated the role of significantly changed metabolites at the animal level.…”

“…Huang et al. performed 16S ribosomal RNA (rRNA) sequencing and untargeted metabolomic profiling of CPP patients; it was revealed that nitric oxide synthesis and Streptococcus were closely associated with CPP ( 19 ). Different from these studies, in this study, we conducted metabolomic analysis of fecal samples of clinical PP girls and animal models and further validated the role of significantly changed metabolites at the animal level.…”

Exploring the Mechanistic Interplay between Gut Microbiota and Precocious Puberty: A Narrative Review

“…Among them, girls with CPP showed increased alpha diversity in their gut microbiota, significant increases in bacteria, such as Alistipes , Klebsiella , and Sutterella , and enhanced inter-bacterial correlations [ 7 ]. Another cross-sectional study demonstrated significant differences in gut microbiota and metabolites between children with CPP and healthy controls, with the Streptococcus genus potentially serving as a candidate molecular marker for CPP treatment [ 103 ]. Similarly, in an observational study, fecal samples from 25 girls with idiopathic CPP and 23 healthy girls were subjected to 16S rDNA sequencing to compare microbial compositions between the groups.…”

“…Moreover, several observational studies have shown associations between nitric oxide synthesis and the progression of precocious puberty [ 103 ]. Functional predictions of the gut microbiota in girls with CPP show increased nitric oxide synthesis and positive correlation with FSH and insulin in children with CPP [ 7 ].…”

“…Moreover, several observational studies have shown associations between nitric oxide synthesis and the progression of precocious puberty [103]. Functional predictions…”