PP can affect children's physical and mental health [17] by increasing the incidence of obesity, cardiovascular disease and metabolic diseases [18], which caused by complex factors. The gut microbiome has been confirmed to be one of the potential factors that associated with the occurrence of PP [14, 15]. In this study, for the first time we looked into the relationship between GM and subgroups of the PP, including ICPP and PPP. We found that the GM composition and function of ICPP and PPP children is significantly different from health children.
Firstly, the abundance of some beneficial bacteria in ICPP and PPP children was declined. The current study found that the abundance of Bacteroides in the GM of children with ICPP significantly decreased, and Bacteroides also less abundant in PPP children though no significance was shown. Studies have confirmed that Bacteroides can degrade plant polysaccharides which cannot be digested by human body and provide 10%-15% of the energy from food [19]. The production of short chain fatty acid, such as propionic acid, will be declined along the reduction of the abundance of Bacteroides [20], leading the increasing of ghrelin secretion [21], and further promoting the secretion of GnRH and the synthesis and transformation of sex hormones [22, 23]. What’s more, the decreasing trend of Bacteroides was shown from HC to PPP, and to ICPP, which corresponded with the development of PP. In addition, Faecalibacterium also presented a significantly decreasing in PPP group than that in HC group. Faecalibacterium prausnitzii, the sole known species belongs to Faecalibacterium, represent more than 5% abundant in the intestine of healthy people, and the lower level of F. prausnitzii is associated with metabolic diseases, such as obesity and diabetes [24], which is a common symptom appeared in precocious puberty children. Even the intestinal transplantation of F. prausnitzii were applied to prevent diabetes [25] Therefore, the declined abundance of Bacteroides and Faecalibacterium would be a key factor of GM linking to the occurrence and development of PP.
Secondly, the abundance of some butyric acid-producing bacteria and conditional pathogenic bacteria in ICPP and PPP children increased. Compared with the HC group, Prevotella, Lachnospiracea incertae sedis, Roseburia, Ruminococcus and Alistipes were enriched in the intestines of children in the PPP and ICPP groups. Studies have confirmed that Prevotella, Lachnospiracea incertae sedis and Roseburia can break down carbohydrates into short-chain fatty acids and participate in butyrate production [26–28]. Also, Ruminococcus is positively correlated with the butyric acid ratio in large intestine [29] In addition, Alistipes is closely related to high-sugar and high-fat diets [30, 31], and PP children prefer high-sugar and high-fat diets [32]. This result further confirms that changes in the diet of PP children affect the composition of GM. Furthermore, the abundance of Alistipes is closely related to the frequency of abdominal pain, which may cause intestinal inflammation [33]. Both butyrate and intestinal inflammation will stimulate insulin secretion and further enhances the transcription of GnRH gene by upregulating the mitogen-activated protein kinase pathway. The hypothalamus will respond the increased expression of GnRH with increasing levels of androgens and LH secretion [34–36]. The increased abundance of Alistipes, can secrete neurotransmission-related metabolites, such as acetic acid, serotonin and dopamine, then activates Hypothalamic-Pituitary-Gonadal Axis (HPGA) to trigger early puberty [15, 37, 38].
The GM symbiosis networks constructed in this study showed the negative correlations between the bacteria (such as Bacteroides and Faecalibacterium) enriched in healthy children and bacteria enriched in ICPP/PPP patients (such as Prevotella, Lachnospiracea incertae sedis, Roseburia, Ruminococcus and Alistipes). These antagonistic relationships indicated that the dominant growth of beneficial bacteria may inhibit the overgrowth of butyric acid-producing bacteria in mature GM individuals, and further keep the normal development of sexual maturity. Hence, we speculated that the abundance Bacteroides, Faecalibacterium and butyric acid-producing bacteria and the relationship between them may be the main contributor for the early puberty development.
The GM function was also predicted in this study, and the result manifested that the metabolic patterns of the GM were significantly different between the ICPP, PPP and HC groups indicating that changes in the composition of GM result in the differences of function. Compared with the HC group, abnormal metabolic pathways related to cell motility, signal transduction, and environmental adaptation were all enriched in the ICPP and PPP children GM functions, while the high-sugar diets related pathway carbohydrate metabolism was reduced. The results remind that high-sugar intake should be limited in the clinical for PP children. Additionally, the identical significant change of the GM functional pathways mentioned above confirmed that these pathways played important roles in the development of PP, and may be the potential treatment targets.