Children with idiopathic short stature have significantly different gut microbiota than their normal height siblings: a case-control study

Liora Lazar, Adi Eshel, Lelyan Moadi, Michal Yackobovitch-Gavan, Meytal Bar-Maisels, Biana Shtaif, Michal Nevo, Moshe Phillip, Sondra Turjeman, Omry Koren, Galia Gat-Yablonski

Research output: Contribution to journalArticlepeer-review


Objectives: To investigate the role of gut microbiota (GM) in pathogenesis of idiopathic short stature (ISS) by comparing GM of ISS children to their normal-height siblings. Methods: This case-control study, conducted at the Schneider Children’s Medical Center’s Institute for Endocrinology and Diabetes between 4/2018-11/2020, involved 30 pairs of healthy pre-pubertal siblings aged 3-10 years, each comprising one sibling with ISS and one with normal height. Outcome measures from fecal analysis of both siblings included GM composition analyzed by 16S rRNA sequencing, fecal metabolomics, and monitoring the growth of germ-free (GF) mice after fecal transplantation. Results: Fecal analysis of ISS children identified higher predicted levels of genes encoding enzymes for pyrimidine, purine, flavin, coenzyme B, and thiamine biosynthesis, lower levels of several amino acids, and a significantly higher prevalence of the phylum Euryarchaeota compared to their normal-height siblings (p<0.001). ISS children with higher levels of Methanobrevibacter, the dominant species in the archaeal gut community, were significantly shorter in stature than those with lower levels (p=0.022). Mice receiving fecal transplants from ISS children did not experience stunted growth, probably due to the eradication of Methanobrevibacter caused by exposure to oxygen during fecal collection. Discussion: Our findings suggest that different characteristics in the GM may explain variations in linear growth. The varying levels of Methanobrevibacter demonstrated within the ISS group reflect the multifactorial nature of ISS and the potential ability of the GM to partially explain growth variations. The targeting of specific microbiota could provide personalized therapies to improve growth in children with ISS.

Original languageEnglish
Article number1343337
JournalFrontiers in Endocrinology
StatePublished - 2024

Bibliographical note

Publisher Copyright:
Copyright © 2024 Lazar, Eshel, Moadi, Yackobovitch-Gavan, Bar-Maisels, Shtaif, Nevo, Phillip, Turjeman, Koren and Gat-Yablonski.


The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was funded by a grant from Pfizer. Inc. (grant # 66197339). The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Acknowledgments

FundersFunder number


    • children
    • germ-free mice
    • gut metabolome
    • gut microbiota
    • idiopathic short stature
    • methanobrevibacter


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