■通过比较特发性身材矮小(ISS)儿童与正常身高兄弟姐妹的肠道菌群(GM)在ISS发病机理中的作用。
■本病例对照研究,在施耐德儿童医学中心内分泌和糖尿病研究所进行4/2018-11/2020,涉及30对3-10岁健康的青春期前兄弟姐妹,每个人都包括一个拥有国际空间站的兄弟姐妹和一个具有正常身高的兄弟姐妹。来自两个兄弟姐妹的粪便分析的结果测量包括通过16SrRNA测序分析的GM组成,粪便代谢组学,并监测粪便移植后无菌(GF)小鼠的生长。
■对ISS儿童的粪便分析确定了更高的预测水平的编码嘧啶酶的基因,嘌呤,黄素,辅酶B,和硫胺素生物合成,较低水平的几种氨基酸,与正常身高的兄弟姐妹相比,欧洲古细菌门的患病率明显更高(p<0.001)。ISS甲氧西林杆菌水平较高的儿童,古细菌肠道群落中的优势物种,在身材上明显短于那些水平较低的人(p=0.022)。接受ISS儿童粪便移植的小鼠没有发育迟缓,可能是由于在粪便收集过程中暴露于氧气引起的甲氧杆菌的根除。
■我们的研究结果表明,GM的不同特征可能解释线性增长的变化。ISS组中显示的不同水平的Methanobrevibacter反映了ISS的多因素性质以及GM部分解释生长变化的潜在能力。特定微生物群的靶向可以提供个性化治疗,以改善ISS儿童的生长。
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
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.
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.