Table_2_Prenatal lead exposure is negatively associated with the gut microbiome in childhood.pdf

BackgroundMetal exposures are associated with gut microbiome (GM) composition and function, and exposures early in development may be particularly important. Considering the role of the GM in association with many adverse health outcomes, understanding the relationship between prenatal metal exposures and the GM is critically important. However, there is sparse knowledge of the association between prenatal metal exposure and GM later in childhood.
ObjectivesThis analysis aims to identify associations between prenatal lead (Pb) exposure and GM composition and function in children 9–11 years old.
MethodsData come from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort based in Mexico City, Mexico. Prenatal metal concentrations were measured in maternal whole blood drawn during the second and third trimesters of pregnancy. Stool samples collected at 9–11 years old underwent metagenomic sequencing to assess the GM. This analysis uses multiple statistical modeling approaches, including linear regression, permutational analysis of variance, weighted quantile sum regression (WQS), and individual taxa regressions, to estimate the association between maternal blood Pb during pregnancy and multiple aspects of the child GM at 9–11 years old, adjusting for relevant confounders.
ResultsOf the 123 child participants in this pilot data analysis, 74 were male and 49 were female. Mean prenatal maternal blood Pb was 33.6 (SE = 2.1) ug/L and 34.9 (SE = 2.1) ug/L at second and third trimesters, respectively. Analysis suggests a consistent negative relationship between prenatal maternal blood Pb and the GM at age 9–11, including measures of alpha and beta diversity, microbiome mixture analysis, and individual taxa. The WQS analysis showed a negative association between prenatal Pb exposure and the gut microbiome, for both second and third trimester exposures (2Tβ = −0.17, 95%CI = [−0.46,0.11]; 3Tβ = −0.17, 95%CI = [−0.44,0.10]). Ruminococcus gnavus, Bifidobacterium longum, Alistipes indistinctus, Bacteroides caccae, and Bifidobacterium bifidum all had weights above the importance threshold from 80% or more of the WQS repeated holdouts in association with both second and third trimester Pb exposure.
DiscussionPilot data analysis suggests a negative association between prenatal Pb exposure and the gut microbiome later in childhood; however, additional investigation is needed.

背景：金属暴露与肠道微生物组（gut microbiome, GM）的组成及功能密切相关，而发育早期的金属暴露或许发挥着尤为关键的作用。鉴于肠道微生物组与诸多不良健康结局存在关联，阐明产前金属暴露与肠道微生物组之间的内在联系至关重要。然而，目前学界对于产前金属暴露与儿童后期肠道微生物组之间的关联仍知之甚少。
研究目的：本分析旨在明确9~11岁儿童产前铅（lead, Pb）暴露与肠道微生物组组成及功能之间的关联。
研究方法：本研究数据来源于墨西哥城的肥胖、生长发育、环境与社会应激编程研究（Programming Research in Obesity, Growth, Environment and Social Stressors, PROGRESS）队列。研究人员在孕妇妊娠中期与妊娠晚期采集的全血样本中检测了产前金属浓度。儿童在9~11岁时收集的粪便样本经宏基因组测序以评估其肠道微生物组。本分析采用多种统计建模方法，包括线性回归、置换方差分析、加权分位数和回归（weighted quantile sum regression, WQS）以及单个类群回归，以估算妊娠期间孕妇血铅水平与儿童9~11岁时肠道微生物组多方面特征的关联，并对相关混杂因素进行校正。
研究结果：本次预试验数据分析共纳入123名儿童参与者，其中男性74名，女性49名。妊娠中期与妊娠晚期孕妇的平均血铅水平分别为33.6（标准误=2.1）μg/L和34.9（标准误=2.1）μg/L。分析结果显示，产前孕妇血铅水平与儿童9~11岁时的肠道微生物组存在持续的负相关关系，涉及α多样性与β多样性测度、微生物组混合物分析以及单个类群回归分析。加权分位数和回归（WQS）分析表明，无论妊娠中期还是晚期暴露，产前铅暴露与肠道微生物组均呈负相关（中期β=-0.17，95%置信区间=[-0.46, 0.11]；晚期β=-0.17，95%置信区间=[-0.44, 0.10]）。在与妊娠中晚期铅暴露的关联分析中，格氏瘤胃球菌（Ruminococcus gnavus）、长双歧杆菌（Bifidobacterium longum）、模糊阿里斯梯斯菌（Alistipes indistinctus）、粪便拟杆菌（Bacteroides caccae）以及两歧双歧杆菌（Bifidobacterium bifidum）的权重在80%及以上的WQS重复留一法分析中均超过了重要性阈值。
讨论：本次预试验数据分析结果表明，产前铅暴露与儿童后期肠道微生物组之间存在负相关关系，但仍需开展进一步的研究以验证该结论。