Francis Ellen C, Hunt Kelly J, Grobman William A, Skupski Daniel W, Mani Ashika, Hinkle Stefanie N
Department of Biostatistics & Epidemiology, Rutgers School of Public Health, Piscataway, NJ 08854, USA.
Public Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.
Metabolites. 2024 Oct 25;14(11):574. doi: 10.3390/metabo14110574.
Approximately one-third of pregnant individuals in the U.S. are affected by obesity, which can adversely impact the in utero environment and offspring. This study aimed to investigate the differences in urine metabolomics between children exposed and unexposed to maternal obesity. In a study nested within a larger pregnancy cohort of women-offspring pairs, we measured untargeted metabolomics using liquid chromatography-mass spectrometry in urine samples from 68 children at 4-8 years of age. We compared metabolite levels between offspring exposed to maternal obesity (body mass index [BMI] ≥ 30.0 kg/m) vs. unexposed (maternal BMI 18.5-24.9 kg/m) and matched them on covariates, using two-sample t-tests, with additional sensitivity analyses based on children's BMI. This study reports statistically significant results ( ≤ 0.05) and potentially noteworthy findings (fold change > 1 or 0.05 < < 0.15), considering compounds' involvement in common pathways or similar biochemical families. The mean (SD) maternal age at study enrollment was 28.0 (6.3) years, the mean child age was 6.6 (0.8) years, 56% of children were male, and 38% of children had a BMI in the overweight/obese range (BMI ≥ 85th percentile). Children exposed to maternal obesity had lower levels of 5-hydroxyindole sulfate and 7-hydroxyindole sulfate and higher levels of secondary bile acids. Phenylacetic acid derivatives were lower in offspring exposed to obesity and in offspring who had a current BMI in the overweight/obese range. Exposure to maternal obesity was associated with lower levels of androgenic steroid dehydroepiandrosterone sulfate (DHEA-S). In this preliminary study, children exposed to maternal obesity in utero had differences in microbiome-related metabolites in urine suggestive of altered microbial catabolism of tryptophan and acetylated peptides. Some of these differences were partially attributable to the offspring's current BMI status. This study highlights the potential of urine metabolomics to identify biomarkers and pathways impacted by in utero exposure to maternal obesity.
在美国，约三分之一的孕妇受肥胖影响，这可能对子宫内环境和后代产生不利影响。本研究旨在调查暴露于和未暴露于母体肥胖的儿童之间尿液代谢组学的差异。在一项嵌套于更大的母婴对妊娠队列研究中，我们使用液相色谱 - 质谱法对68名4至8岁儿童的尿液样本进行了非靶向代谢组学测量。我们比较了暴露于母体肥胖（体重指数[BMI]≥30.0 kg/m²）与未暴露（母体BMI 18.5 - 24.9 kg/m²）的后代之间的代谢物水平，并根据协变量进行匹配，使用双样本t检验，并基于儿童的BMI进行了额外的敏感性分析。本研究报告了具有统计学意义的结果（P≤0.05）和潜在值得关注的发现（倍数变化>1或0.05<P<0.15），同时考虑了化合物参与的常见途径或相似生化家族。研究入组时母体的平均（标准差）年龄为28.0（6.3）岁，儿童平均年龄为6.6（(0.8)）岁，56%的儿童为男性，38%的儿童BMI处于超重/肥胖范围（BMI≥第85百分位数）。暴露于母体肥胖的儿童5 - 羟基吲哚硫酸盐和7 - 羟基吲哚硫酸盐水平较低，次级胆汁酸水平较高。肥胖暴露后代和当前BMI处于超重/肥胖范围的后代中苯乙酸衍生物水平较低。暴露于母体肥胖与硫酸脱氢表雄酮（DHEA - S）这种雄激素类固醇水平较低有关。在这项初步研究中，子宫内暴露于母体肥胖的儿童尿液中微生物群相关代谢物存在差异，提示色氨酸和乙酰化肽的微生物分解代谢发生改变。其中一些差异部分归因于后代当前的BMI状态。本研究强调了尿液代谢组学在识别受子宫内暴露于母体肥胖影响的生物标志物和途径方面的潜力。
