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Characteristics of intestinal microbiota in children with idiopathic short stature: a cross-sectional study

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Abstract

Idiopathic short stature (ISS) accounts for more than 70% of childhood short stature cases, with an undefined etiology and pathogenesis, leading to limited treatment. However, recent studies have shown that intestinal microbiota may be associated with ISS. This study aimed to characterize the intestinal microbiota in children with ISS, effect of treatment with growth hormones, and association between specific bacterial species and ISS. This study enrolled 55 children, comprising 40 diagnosed with ISS at Jinhua Hospital, Zhejiang University, and 15 healthy controls. The subjects with ISS were divided into the untreated ISS group (UISS group, 22 children who had not been treated with recombinant human growth hormone [rhGH]), treated ISS group (TISS group, 18 children treated with rhGH for 1 year), and control group (NC group, 15 healthy children). High-throughput sequencing was used to determine the intestinal microbiota characteristics. Higher abundances of Bacteroides, Prevotella, Alistipes, Parabacteroides, Agathobacter and Roseburia were found in the UISS and TISS groups than in the control group, whereas Bifidobacterium, Subdoligranulum, and Romboutsia were less abundant. The composition of intestinal microbiota in the UISS and TISS groups was almost identical, except for Prevotella. The TISS group had significantly lower levels of Prevotella than did the UISS group, which were closer to those of the NC group. Receiver operating characteristic curve analysis revealed that the abundances of Prevotella, Bifidobacterium, Bacteroides, and Subdoligranulum were effective in differentiating between the UISS and NC groups.

Conclusion: Alterations in intestinal microbiota may be associated with ISS. Specific bacterial species, such as Prevotella, may be potential diagnostic markers for ISS.

What is Known:

• ISS is associated with the GH-IGF-1 axis.

• Recent studies indicated an association between the GH-IGF-1 axis and intestinal microbiota.

What is New:

• Children with ISS showed alterations in intestinal microbiota, with a relative increase in the abundance of gut inflammation-related bacteria.

• The relative abundances of Prevotella, Bacteroides, Bifidobacterium, and Subdoligranulum may serve as potential diagnostic markers.

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Data availability statement

The datasets presented in this paper can be found in online repositories. The names of the repositories and their accession numbers can be found in the NCBI Sequence Read Archive database [accession number PRJNA879917]. https://www.ncbi.nlm.nih.gov/bioproject/PRJNA879917.

Abbreviations

ASV:

Amplicon sequence variant

AUC:

Area under the curve

BMI:

Body mass index

cAMP:

Cyclic adenosine monophosphate

CCDI:

Chinese children dietary index

DNA:

Deoxyribonucleic acid

FFQ:

Food frequency questionnaire

GH:

Growth hormone

GH-IGF-1 axis:

Growth hormone- insulin-like growth factor-1 axis

IGF-1:

Insulin-like growth factor-1

IQR:

Interquartile ranges

ISS:

Idiopathic short stature

LefSe:

Linear discriminant analysis of effect size

NC group:

Control group

NMDS:

Nonmetric multidimensional scaling

PCoA:

Principal coordinate analysis

PCR:

Polymerase chain reaction

rhGH:

Recombinant human growth hormone

ROC:

Receiver operating characteristic

SCFA:

Short-chain fatty acids

TISS group:

Treated ISS group

UISS group:

Untreated ISS group

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Acknowledgements

We would like to thank Editage (www.editage.cn) for English language editing.

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Authors and Affiliations

  1. Department of Pediatrics, Jinhua Hospital, Zhejiang University and Jinhua Municipal Central Hospital, Jinhua, China

    Jing Miao, Panjian Lai, Kan Wang, Guoxing Fang, Xiaobing Li, Linqian Zhang & Yunguang Bao

  2. Department of Pediatrics, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China

    Jing Miao & Mizu Jiang

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Contributions

Jing Miao and Panjian Lai participated in and approved the manuscript. Mizu Jiang and Yunguang Bao contributed to the project concept and design, analyzed the data, and wrote the first draft of the manuscript. Linqian Zhang, Kan Wang, Guoxing Fang, and Xiaobing Li performed the data acquisition and analysis. All the authors commented on previous versions the manuscript. All authors read and approved the final version.

Corresponding author

Correspondence to Yunguang Bao.

Ethics declarations

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Jinhua Hospital, Zhejiang University (2019-014-001).

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Written informed consent was obtained from the guardians.

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

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Communicated by Gregorio Milani

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Table S1:

The relative abundance of each bacterial at phylum, class, order, family and genus levels. (DOCX 63 KB)

Fig. S1

The sequence number distribution diagram. (TIF 491 KB)

Fig. S2

The quality scores of bases. (TIF 3860 KB)

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Miao, J., Lai, P., Wang, K. et al. Characteristics of intestinal microbiota in children with idiopathic short stature: a cross-sectional study. Eur J Pediatr 182, 4537–4546 (2023). https://doi.org/10.1007/s00431-023-05132-8

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