PDF(Pubmed)
Abstract：
BACKGROUND: Idiopathic short stature (ISS) is characterized by short stature with unknown causes. Recent studies showed different gut microbiota flora and reduced fecal short-chain fatty acids in ISS children. However, the roles of the microbiome and metabolites in the pathogenesis of ISS remains largely unknown.
METHODS: We recruited 51 Chinese subjects, comprising 26 ISS children and 25 normal-height control individuals. Untargeted metabolomics was performed to explore the fecal metabolic profiles between groups. A shotgun metagenomic sequencing approach was used to investigate the microbiome at the strains level. Mediation analyses were done to reveal correlations between the height standard deviation (SD) value, the gut microbiome and metabolites.
RESULTS: We detected marked differences in the composition of fecal metabolites in the ISS group, particularly a significant increase in erucic acid and a decrease in spermidine, adenosine and L-5-Hydroxytryptophan, when compared to those of controls. We further identified specific groups of bacterial strains to be associated with the different metabolic profile. Through mediation analysis, 50 linkages were established. KEGG pathway analysis of microbiota and metabolites indicated nutritional disturbances. 13 selected features were able to accurately distinguish the ISS children from the controls (AUC = 0.933 [95%CI, 79.9-100%]) by receiver operating characteristic (ROC) analysis.
CONCLUSIONS: Our study suggests that the microbiome and the microbial-derived metabolites play certain roles in children\'s growth. These findings provide a new research direction for better understanding the mechanism(s) underlying ISS.
METHODS: We recruited 51 Chinese subjects, comprising 26 ISS children and 25 normal-height control individuals. Untargeted metabolomics was performed to explore the fecal metabolic profiles between groups. A shotgun metagenomic sequencing approach was used to investigate the microbiome at the strains level. Mediation analyses were done to reveal correlations between the height standard deviation (SD) value, the gut microbiome and metabolites.
RESULTS: We detected marked differences in the composition of fecal metabolites in the ISS group, particularly a significant increase in erucic acid and a decrease in spermidine, adenosine and L-5-Hydroxytryptophan, when compared to those of controls. We further identified specific groups of bacterial strains to be associated with the different metabolic profile. Through mediation analysis, 50 linkages were established. KEGG pathway analysis of microbiota and metabolites indicated nutritional disturbances. 13 selected features were able to accurately distinguish the ISS children from the controls (AUC = 0.933 [95%CI, 79.9-100%]) by receiver operating characteristic (ROC) analysis.
CONCLUSIONS: Our study suggests that the microbiome and the microbial-derived metabolites play certain roles in children\'s growth. These findings provide a new research direction for better understanding the mechanism(s) underlying ISS.
摘要：
背景：特发性身材矮小（ISS）的特征是原因不明的身材矮小。最近的研究表明，ISS儿童的肠道菌群不同，粪便短链脂肪酸减少。然而,微生物组和代谢产物在ISS发病机制中的作用在很大程度上仍然未知.
方法：我们招募了51名中国受试者，包括26名ISS儿童和25名正常身高控制人。进行非靶向代谢组学以探索组间的粪便代谢谱。使用鸟枪宏基因组测序方法来研究菌株水平的微生物组。进行了中介分析，以揭示高度标准偏差(SD)值之间的相关性，肠道微生物组和代谢产物。
结果：我们检测到ISS组中粪便代谢物组成的显着差异，特别是芥酸的显着增加和亚精胺的减少，腺苷和L-5-羟基色氨酸，与对照组相比。我们进一步鉴定了与不同代谢谱相关的特定细菌菌株组。通过调解分析,建立了50个联系。对微生物群和代谢产物的KEGG途径分析表明营养紊乱。通过受试者工作特征（ROC）分析，13个选定的特征能够准确区分ISS儿童与对照组（AUC=0.933[95CI，79.9-100％]）。
结论：我们的研究表明，微生物组和微生物衍生的代谢产物在儿童的生长中起着一定的作用。这些发现为更好地理解ISS的潜在机制提供了新的研究方向。
方法：我们招募了51名中国受试者，包括26名ISS儿童和25名正常身高控制人。进行非靶向代谢组学以探索组间的粪便代谢谱。使用鸟枪宏基因组测序方法来研究菌株水平的微生物组。进行了中介分析，以揭示高度标准偏差(SD)值之间的相关性，肠道微生物组和代谢产物。
结果：我们检测到ISS组中粪便代谢物组成的显着差异，特别是芥酸的显着增加和亚精胺的减少，腺苷和L-5-羟基色氨酸，与对照组相比。我们进一步鉴定了与不同代谢谱相关的特定细菌菌株组。通过调解分析,建立了50个联系。对微生物群和代谢产物的KEGG途径分析表明营养紊乱。通过受试者工作特征（ROC）分析，13个选定的特征能够准确区分ISS儿童与对照组（AUC=0.933[95CI，79.9-100％]）。
结论：我们的研究表明，微生物组和微生物衍生的代谢产物在儿童的生长中起着一定的作用。这些发现为更好地理解ISS的潜在机制提供了新的研究方向。
