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Precocious puberty and gut microbiome: a systematic review and meta-analysis

Pediatric Research (2025)Cite this article

Abstract

Central precocious puberty (CPP) is a condition that affects prepubertal children, particularly girls. Recent evidence suggests an association between the gut microbiome (GM) and CPP. This study aims to explore this association. We analyzed data from studies investigating the association between GM and CPP. Various databases were searched for relevant articles published from database inception to December 31, 2023. Standardized mean difference values were calculated and depicted in forest plots. Furthermore, subgroup analyses by type of study subject (animals vs. humans) were performed. The final analysis included 9 studies. Five were human studies, whereas the remaining four were animal (rats or mice) studies. In the precocious puberty group, the abundances (at the genus level) of Holdemania, Roseburia, Alistipes, Dialister, Enterococcus, Ruminococcus, Bilophila, and Lachnoclostridium increased significantly, whereas those of Bacteroides, Anaerostipes, Megamonas, and Gemella decreased significantly. Furthermore, for this group, the Shannon index for alpha diversity was increased in human studies and decreased in animal studies compared to the control group. Notably, the levels of major short-chain fatty acids, butyric and propionic acids, were significantly reduced in the precocious puberty group. There was an association between CPP and GM. Both subgroups revealed that microbiome profiles vary across individuals with precocious puberty.

Impact

  • To our knowledge, this is the first systematic review and meta-analysis to explore the association between the gut microbiome and precocious puberty in both human and animal models.

  • Our findings reveal distinct microbial patterns in individuals with CPP, including consistent alterations in 12 bacterial genera and significant changes in short-chain fatty acid levels.

  • By identifying reproducible microbial signatures and metabolites associated with CPP, this study lays the groundwork for microbiome-targeted interventions alongside traditional hormonal therapies.

  • The study addresses key methodological inconsistencies in existing literature, highlighting the need for standardized protocols in future research on the gut-puberty axis.

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Fig. 1: PRISMA flowchart depicting study selection.
Fig. 2: Forest plot for the association between PP and OTU count.
Fig. 3: Forest plot for the association between PP and Shannon alpha diversity index.
Fig. 4: Forest plot for the association between PP and SCFAs.

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Data availability

Data were extracted from papers and supplementary information published online. All data are available online. The data sets used in the present study are also available from the corresponding author upon reasonable request.

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Acknowledgements

This manuscript was edited by Wallace Academic Editing. We acknowledge the use of ChatGPT for refining the manuscript.

Funding

This study was supported by the National Science and Technology Council (grant numbers: MOST110-2628-B-038-014–111, NSTC 112-2628-B-038-005, NSTC 114-2622-B-038-003 [from Yang-Ching Chen]), as well as by the Taipei Medical University and National Defense University Medical Joint Research Program (114_T&N_04).

Author information

Authors and Affiliations

  1. College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC

    José Roberto Rodríguez Mazariegos & Nguyen Nhat Nam

  2. Faculty of Health Sciences, Rafael Landivar University, Guatemala, Guatemala

    José Roberto Rodríguez Mazariegos

  3. School of Grassland Science, Beijing Forestry University, Beijing, China

    Tingbei Bo

  4. School of Life Sciences, Shandong University, Qingdao, China

    Dehua Wang

  5. Department of Family Medicine, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan, ROC

    Jhih-Wei Hsu & Yang-Ching Chen

  6. Department of Family Medicine, School of Medicine, College of medicine, Taipei Medical University, Taipei, Taiwan, ROC

    Yang-Ching Chen

  7. School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan, ROC

    Yang-Ching Chen

  8. Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei, Taiwan, ROC

    Yang-Ching Chen

  9. Nutrition Research Center, Taipei Medical University Hospital, Taipei, Taiwan, ROC

    Yang-Ching Chen

Authors
  1. José Roberto Rodríguez Mazariegos
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  2. Nguyen Nhat Nam
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  3. Tingbei Bo
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  4. Dehua Wang
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  5. Jhih-Wei Hsu
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Contributions

Yang-Ching Chen: Conceptualization, Design, Manuscript revision, and Supervision. José Roberto Rodríguez Mazariegos: Systematic search, Study selection, Risk-of-bias assessment, Data extraction, Data analysis, Data interpretation, and Manuscript preparation—writing. Nguyen Nhat Nam: Systematic search, Study selection, Risk-of-bias assessment, Data extraction, and Manuscript revision. Tingbei Bo and Dehua Wang: Data collection. Jhih-Wei Hsu: Manuscript revision. All authors have reviewed and approved the final version of the manuscript and agreed to take responsibility for all aspects of the work.

Corresponding author

Correspondence to Yang-Ching Chen.

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Conflict of interest

No financial or non-financial benefits have been received or will be received from any party related to directly or indirectly to the subject of this article.

Consent statement

This study synthesizes data from previously published research, no new data were collected from human participants. Specifically, no new data were collected from the TPLS for this meta-analysis. The data used from the TPLS were previously gathered as part of earlier IRB-approved studies. As a result, informed consent was not required for this study.

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Rodríguez Mazariegos, J.R., Nam, N.N., Bo, T. et al. Precocious puberty and gut microbiome: a systematic review and meta-analysis. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04180-0

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