Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
Department of Earth Sciences, Dartmouth College, Hanover, NH, USA.
Environ Int. 2020 May;138:105613. doi: 10.1016/j.envint.2020.105613. Epub 2020 Mar 3.
The infant microbiome contributes to health status across the lifespan, but environmental factors affecting microbial communities are poorly understood, particularly when toxic and essential elements interact.
We aimed to identify the associations between a spectrum of other early-postnatal nutrient or toxic elemental exposures measured and the infant gut microbiome.
Our analysis included 179 six-week-old infants from the New Hampshire Birth Cohort Study. Eleven elements were measured in infant toenail clippings. The gut microbiome was assessed using 16S rRNA V4-V5 hypervariable region targeted sequencing. Multivariable zero-inflated logistic normal regression (MZILN) was used to model the association between element concentrations and taxon relative abundance. To explore interactive and nonlinear associations between the exposures and specific taxa we employed Bayesian Kernel Machine Regression (BKMR). Effect modification by delivery mode, feeding mode, peripartum antibiotic exposure, and infant sex was assessed with stratified models.
We found a negative association between arsenic and microbial diversity in the full population that was accentuated among infants exposed to peripartum antibiotics. Arsenic, cadmium, copper, iron, lead, manganese, nickel, selenium, tin, and zinc were each associated with differences in at least one taxon in the full study population, with most of the related taxa belonging to the Bacteroides and Lactobacillales. In stratified analyses, mercury, in addition to the other elements, was associated with specific taxa. Bifidobacterium, which associated negatively with zinc in MZILN and BKMR models, had a quadratic association with arsenic concentrations. These associations varied with the concentration of the other element.
Early postnatal toxic and nutrient elemental exposures are associated with differences in the infant microbiome. Further research is needed to clarify the whether these alterations are a biomarker of exposure or if they have implications for child and lifelong health.
婴儿微生物组对整个生命周期的健康状况都有影响，但人们对影响微生物群落的环境因素知之甚少，尤其是在有毒元素和必需元素相互作用时。
我们旨在确定在 11 种婴儿出生后早期营养素或有毒元素暴露测量值与婴儿肠道微生物组之间的关联。
我们的分析包括新罕布什尔州出生队列研究中的 179 名 6 周龄婴儿。在婴儿的脚趾甲屑中测量了 11 种元素。使用 16S rRNA V4-V5 高变区靶向测序评估肠道微生物组。采用多变量零膨胀逻辑正态回归（MZILN）对元素浓度与分类群相对丰度之间的关系进行建模。为了探索暴露与特定分类群之间的交互和非线性关联，我们采用了贝叶斯核机器回归（BKMR）。通过分层模型评估了分娩方式、喂养方式、围产期抗生素暴露和婴儿性别对效应的修饰作用。
我们发现砷与全人群微生物多样性呈负相关，而在暴露于围产期抗生素的婴儿中这种相关性更为明显。砷、镉、铜、铁、铅、锰、镍、硒、锡和锌都与全人群研究中至少一个分类群的差异有关，大多数相关的分类群属于拟杆菌门和乳杆菌目。在分层分析中，除了其他元素外，汞还与特定的分类群有关。在 MZILN 和 BKMR 模型中与锌呈负相关的双歧杆菌与砷浓度呈二次关联。这些关联随其他元素浓度的变化而变化。
婴儿出生后早期有毒和营养元素暴露与婴儿微生物组的差异有关。需要进一步研究以明确这些变化是暴露的生物标志物，还是对儿童和终身健康有影响。
