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Impact of different growth hormone levels on gut microbiota and metabolism in short stature

Pediatric Research (2024)Cite this article

Abstract

Background

Growth hormone deficiency(GHD) and idiopathic short stature(ISS) are the primary causes of short stature in children. Animal experiments have revealed a link between growth hormone(GH), gut microbiota and metabolism, however, limited information is available from human trials.

Methods

Fecal samples collected from GHD (n = 36), ISS (n = 32) and healthy control (HC) children(n = 16) were subjected to microbiome (16 S rRNA gene sequencing) and metabolome (nuclear magnetic resonance,NMR) analyses.

Results

GHD, ISS and HC exhibit distinct differences in beta diversity of gut microbiota.In addition, short stature (GHD and ISS) exhibit higher relative abundance of Prevotellaceae_NK3B31_group at genus level compared to HC, whereas Rodentibacter, Rothia, and Pelomonas showed lower abundance. Additionally,Fusobacterium_mortiferum was identified as the characteristic species of GHD. Moreover, glucose metabolism, pyruvate metabolism and pyrimidine metabolism might play significant roles for distinguishing between GHD and normal GH groups (ISS and HC). Furthermore, a disease prediction model based on differential bacteria and metabolites between GHD and ISS exhibited high diagnostic value.

Conclusion

These findings highlight the characteristics of different GH levels on the gut microbiota and metabolism in children, providing novel perspectives for early diagnosis and prognostic treatment of short stature with abnormal GH levels.

Impact

  • The key message of our study is to identify human-relevant gut microbiota and host metabolic patterns that are interfered with growth hormone levels, and to develop biomarker models to identify short stature associated with growth hormone deficiency.

  • We used idiopathic short stature as a control group for growth hormone deficiency, complementing the absence of height as a factor in the existing literature.

  • Our study ultimately hopes to shed new light on the diagnosis and treatment of short stature children associated with growth hormone deficiency.

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Fig. 1: Gut microbiome diversity and structure analysis.
Fig. 2: Taxonomic changes of gut microbiota at genus level.
Fig. 3: Metabolic pattern recognition of fecal samples in GHD, ISS, and HC.
Fig. 4: Metabolic pathway impact analysis of fecal metabolites in GHD, ISS, and HC.
Fig. 5: Correlation analysis between gut microbiota, host metabolome and clinical indices.
Fig. 6: ROC analysis of differential metabolites and microbiome biomarkers of GHD and ISS.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

I would like to express my deepest gratitude to all those who contributed to the research. My deepest gratitude goes to Professor Zhihan Yan, Xiaoou Shan, and Hongchang Gao for their invaluable guidance and feedback throughout the entire research process. Their insightful comments and expertise significantly contributed to the improvement of this manuscript. Special thanks to all my fellow classmates who gave me their time in listening to me and helping me work out the difficulties I have encountered in my research. Additionally, I am truly grateful for the continuous support and encouragement received from all those involved in this project. Their commitment to excellence served as a driving force throughout the research process. Without the assistance and contributions of the aforementioned individuals and organizations, this study would not have been possible.

Funding

Our work was supported by grants from the National Natural Science Foundation of China (No. 82100952 and No. 82071902) and Wenzhou Science and Technology Bureau in China (No. Y20220269).

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Author notes

  1. These authors contributed equally: Lan Li, Yu Wang.

Authors and Affiliations

  1. Department of Radiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China

    Lan Li, Yu Wang, Yinyin Huang, Yi Lu, Weiyi Wang, Xian Chen & Zhihan Yan

  2. Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China

    Lan Li & Hongchang Gao

  3. Department of Radiology, First affiliated Hospital of Huzhou University, Huzhou, China

    Lan Li

  4. Wenzhou Key Laboratory of Structural and Functional Imaging, Wenzhou, China

    Yi Lu & Zhihan Yan

  5. Department of Pediatric Endocrinology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China

    Xiaoou Shan

  6. Key Laboratory of Efficacy Evaluation of Traditional Chinese Medicine and encephalopathy research of Zhejiang Province, Wenzhou, China

    Hongchang Gao

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  1. Lan Li
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Contributions

Lan Li, Yu Wang, Yinyin Huang, Yi Lu, Weiyi Wang, and Xian Chen have made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; Lan Li drafted the article and Yi Lu, Zhihan Yan, Hongchang Gao, Xiaoou Shan revised it critically for important intellectual content.

Corresponding authors

Correspondence to Xiaoou Shan, Hongchang Gao or Zhihan Yan.

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The parents of all participants provided written informed consent upon receiving a written explanation of the study’s purpose before enrollment.

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Li, L., Wang, Y., Huang, Y. et al. Impact of different growth hormone levels on gut microbiota and metabolism in short stature. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03140-4

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  • DOI: https://doi.org/10.1038/s41390-024-03140-4

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