Lazar Liora, Eshel Adi, Moadi Lelyan, Yackobovitch-Gavan Michal, Bar-Maisels Meytal, Shtaif Biana, Nevo Michal, Phillip Moshe, Turjeman Sondra, Koren Omry, Gat-Yablonski Galia
School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
Front Endocrinol (Lausanne). 2024 Feb 23;15:1343337. doi: 10.3389/fendo.2024.1343337. eCollection 2024.
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.
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.
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 , 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 caused by exposure to oxygen during fecal collection.
Our findings suggest that different characteristics in the GM may explain variations in linear growth. The varying levels of 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.
通过比较特发性身材矮小（ISS）儿童与其正常身高的同胞的肠道微生物群（GM），研究GM在ISS发病机制中的作用。
本病例对照研究于2018年4月至2020年11月在施耐德儿童医学中心内分泌与糖尿病研究所进行，纳入了30对3至10岁健康的青春期前同胞，每对同胞中一个患有ISS，另一个身高正常。对同胞双方粪便分析的结果指标包括通过16S rRNA测序分析GM组成、粪便代谢组学，以及粪便移植后监测无菌（GF）小鼠的生长情况。
对ISS儿童的粪便分析发现，与身高正常的同胞相比，ISS儿童中编码嘧啶、嘌呤、黄素、辅酶B和硫胺生物合成酶的基因预测水平更高，几种氨基酸水平更低，广古菌门的患病率显著更高（p<0.001）。古菌肠道群落中的优势物种水平较高的ISS儿童，其身高明显低于水平较低的儿童（p=0.022）。接受ISS儿童粪便移植的小鼠没有出现生长发育迟缓，可能是由于粪便收集过程中暴露于氧气导致该菌被根除。
我们的研究结果表明，GM的不同特征可能解释线性生长的差异。ISS组内不同水平的[此处原文可能缺失特定内容]反映了ISS的多因素性质以及GM部分解释生长差异的潜在能力。针对特定微生物群可能提供个性化疗法，以促进ISS儿童的生长。
