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婴儿肠道微生物组和血清代谢组的综合多组学分析揭示了儿童早发性肥胖的关键分子生物标志物。

Integrative multiomics analysis of infant gut microbiome and serum metabolome reveals key molecular biomarkers of early onset childhood obesity.

作者信息

Rafiq Talha, Stearns Jennifer C, Shanmuganathan Meera, Azab Sandi M, Anand Sonia S, Thabane Lehana, Beyene Joseph, Williams Natalie C, Morrison Katherine M, Teo Koon K, Britz-McKibbin Philip, de Souza Russell J

机构信息

Medical Sciences Graduate Program, Faculty of Health Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada.

Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, ON L8L 2X2, Canada.

出版信息

Heliyon. 2023 May 30;9(6):e16651. doi: 10.1016/j.heliyon.2023.e16651. eCollection 2023 Jun.

DOI:10.1016/j.heliyon.2023.e16651
PMID:37332914
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10272340/
Abstract

Evidence supports a complex interplay of gut microbiome and host metabolism as regulators of obesity. The metabolic phenotype and microbial metabolism of host diet may also contribute to greater obesity risk in children early in life. This study aimed to identify features that discriminated overweight/obese from normal weight infants by integrating gut microbiome and serum metabolome profiles. This prospective analysis included 50 South Asian children living in Canada, selected from the SouTh Asian biRth cohorT (START). Serum metabolites were measured by multisegment injection-capillary electrophoresis-mass spectrometry and the relative abundance of bacterial 16S rRNA gene amplicon sequence variant was evaluated at 1 year. Cumulative body mass index (BMI) and skinfold thickness (SSF) scores were calculated from birth to 3 years as the total area under the growth curve (AUC). BMI and/or SSF >85th percentile was used to define overweight/obesity. Data Integration Analysis for Biomarker discovery using Latent cOmponent (DIABLO) was used to identify discriminant features associated with childhood overweight/obesity. The associations between identified features and anthropometric measures were examined using logistic regression. Circulating metabolites including glutamic acid, acetylcarnitine, carnitine, and threonine were positively, whereas γ-aminobutyric acid (GABA), symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) were negatively associated with childhood overweight/obesity. The abundance of the and genera were positively, and stricto 1 and were negatively associated with childhood overweight/obesity. Integrative analysis revealed that was positively whereas was inversely correlated with GABA and SDMA, and was inversely correlated with GABA. This study provides insights into metabolic and microbial signatures which may regulate satiety, energy metabolism, inflammatory processes, and/or gut barrier function, and therefore, obesity trajectories in childhood. Understanding the functional capacity of these molecular features and potentially modifiable risk factors such as dietary exposures early in life may offer a novel approach for preventing childhood obesity.

摘要

有证据支持肠道微生物群与宿主代谢之间存在复杂的相互作用,它们共同作为肥胖的调节因子。宿主饮食的代谢表型和微生物代谢也可能导致儿童在生命早期面临更高的肥胖风险。本研究旨在通过整合肠道微生物群和血清代谢组谱,确定区分超重/肥胖婴儿与正常体重婴儿的特征。这项前瞻性分析纳入了50名居住在加拿大的南亚儿童,他们选自南亚出生队列(START)。血清代谢物通过多段进样-毛细管电泳-质谱法进行测量,并在1岁时评估细菌16S rRNA基因扩增子序列变体的相对丰度。从出生到3岁计算累积体重指数(BMI)和皮褶厚度(SSF)得分,作为生长曲线下的总面积(AUC)。BMI和/或SSF>第85百分位数被用于定义超重/肥胖。使用基于潜在成分的生物标志物发现数据整合分析(DIABLO)来识别与儿童超重/肥胖相关的判别特征。使用逻辑回归检验所识别特征与人体测量指标之间的关联。循环代谢物包括谷氨酸、乙酰肉碱、肉碱和苏氨酸与儿童超重/肥胖呈正相关,而γ-氨基丁酸(GABA)、对称二甲基精氨酸(SDMA)和不对称二甲基精氨酸(ADMA)与儿童超重/肥胖呈负相关。 属和 属的丰度与儿童超重/肥胖呈正相关,而 狭义1属和 属与儿童超重/肥胖呈负相关。综合分析表明, 与GABA和SDMA呈正相关,而与GABA呈负相关, 与GABA呈负相关。本研究提供了关于代谢和微生物特征的见解,这些特征可能调节饱腹感、能量代谢、炎症过程和/或肠道屏障功能,进而影响儿童期的肥胖轨迹。了解这些分子特征的功能能力以及生命早期潜在可改变的风险因素,如饮食暴露,可能为预防儿童肥胖提供一种新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/086a/10272340/73d565476e48/gr5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/086a/10272340/5eea7297139e/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/086a/10272340/18d17835691e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/086a/10272340/d594731513ef/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/086a/10272340/05def5433e9f/gr3.jpg
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