Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
Department of Earth Sciences, Dartmouth College, Hanover, NH, USA.
Environ Res. 2022 Nov;214(Pt 4):114099. doi: 10.1016/j.envres.2022.114099. Epub 2022 Aug 23.
Gut bacteria are at the interface of environmental exposures and their impact on human systems, and may alter host absorption, metabolism, and excretion of toxic chemicals. We investigated whether arsenic-metabolizing bacterial gene pathways related to urinary arsenic concentrations. In the New Hampshire Birth Cohort Study, urine and stool samples were obtained at six weeks (n = 186) and one year (n = 190) of age. Inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and arsenobetaine (AsB) were quantified in infant urine samples using high-performance liquid chromatography with inductively coupled plasma mass spectrometry. Total arsenic exposure (tAs) was summarized as Σ(iAs, MMA, DMA) and log-transformed. Fecal microbial DNA underwent metagenomic sequencing and the relative abundance of bacterial gene pathways were grouped as KEGG Orthologies (KOs) using BioBakery algorithms. Arsenic metabolism KOs with >80% prevalence were log-transformed and modeled continuously using linear regression, those with <10% were not evaluated and those with 10-80% prevalence were analyzed dichotomously (detect/non-detect) using logistic regression. In the first set of models, tAs was regressed against KO relative abundance or detection adjusting for age at sample collection and child's sex. Effect modification by delivery mode was assessed in stratified models. In the second set of models, the association between the relative abundance/detection of the KOs and arsenic speciation (%iAs, %MMA, %DMA) was quantified with linear regression. Urinary tAs was associated with the increased relative abundance/detection odds of several arsenic-related KOs, including K16509, an arsenate reductase transcriptional regulator, with stronger associations among six-week-olds than one-year-olds. K16509 was also associated with decreased %MMA and increased %DMA at six weeks and one year. Notably, many associations were stronger among operatively-delivered than vaginally-delivered infants. Our findings suggest associations between arsenic-metabolizing bacteria in the infant gut microbiome and urinary arsenic excretion.
肠道细菌处于环境暴露及其对人体系统影响的界面，可能改变宿主对有毒化学物质的吸收、代谢和排泄。我们研究了与尿砷浓度相关的砷代谢细菌基因途径是否存在。在新罕布什尔州出生队列研究中，在 6 周（n=186）和 1 年（n=190）时获得尿液和粪便样本。使用高效液相色谱-电感耦合等离子体质谱法测定婴儿尿样中的无机砷（iAs）、一甲基砷酸（MMA）、二甲基砷酸（DMA）和砷甜菜碱（AsB）。总砷暴露（tAs）总结为Σ（iAs、MMA、DMA）并进行对数转换。粪便微生物 DNA 进行宏基因组测序，使用 BioBakery 算法将细菌基因途径的相对丰度分组为 KEGG 同源物（KOs）。具有>80%流行率的砷代谢 KOs 进行对数转换，并使用线性回归连续建模，流行率<10%的 KOs 不进行评估，流行率为 10-80%的 KOs 使用逻辑回归进行二分类（检测/未检测）分析。在第一组模型中，tAs 与 KO 相对丰度或检测值进行回归，调整样本采集时的年龄和儿童性别。通过分层模型评估了分娩方式的效应修饰。在第二组模型中，使用线性回归定量了 KO 的相对丰度/检测与砷形态（%iAs、%MMA、%DMA）之间的关联。尿 tAs 与几种砷相关 KO 的相对丰度/检测比值的增加有关，包括 K16509，一种砷酸盐还原酶转录调节因子，在 6 周龄婴儿中的相关性强于 1 岁婴儿。K16509 还与 6 周和 1 岁时 MMA 减少和 DMA 增加有关。值得注意的是，许多关联在剖腹分娩婴儿中比阴道分娩婴儿更强。我们的研究结果表明，婴儿肠道微生物组中砷代谢细菌与尿砷排泄之间存在关联。
