Contribution of gut bacteria to arsenic metabolism in the first year of life in a prospective birth cohort.

Contribution of gut bacteria to arsenic metabolism in the first year of life in a prospective birth cohort.
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DOI:
10.1016/j.envres.2022.114099
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发表时间:
2022-11
影响因子:
8.3
通讯作者:
Karagas, Margaret R.
Karagas, Margaret R.
中科院分区:
环境科学与生态学2区
文献类型:
--
作者:
Laue, Hannah E.;Moroishi, Yuka;Palys, Thomas J.;Jackson, Brian P.;Madan, Juliette C.;Karagas, Margaret R.

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肠道细菌处于环境暴露及其对人体系统影响的界面,并可能改变宿主对有毒化学物质的吸收、代谢和排泄。我们研究了砷代谢细菌基因通路是否与尿砷浓度相关。在新罕布什尔州出生队列研究中,在6周龄(n = 186)和1岁(n = 190)时采集尿液和粪便样本。采用高效液相色谱-电感耦合等离子体质谱法对婴儿尿样中的无机砷(iAs)、甲基胂酸(MMA)、二甲基胂酸(DMA)和砷甜菜碱(AsB)进行定量。总砷暴露量(tAs)总结为IAs(iAs、MMA、DMA)和log2转换。对粪便微生物DNA进行宏基因组测序,并使用BioBakery算法将细菌基因途径的相对丰度分组为KEGG同源序列(科斯)。对患病率> 80%的砷代谢相关科斯进行log2转换,并使用线性回归连续建模,不评估患病率<10%的患者,使用逻辑回归对患病率为10 - 80%的患者进行二分分析(检测/未检测)。在第一组模型中,tAs针对KO相对丰度或检测进行回归,以调整样品收集时的年龄和儿童性别。在分层模型中评估了分娩方式的效应改变。在第二组模型中,用线性回归定量科斯的相对丰度/检测与砷形态(% iAs、%MMA、%DMA)之间的关联。尿tAs与几种砷相关科斯的相对丰度/检测几率增加相关,包括K16509,一种砷酸还原酶转录调节因子,6周龄儿童的相关性比1岁儿童强。K16509还与6周和1年时的%MMA和%DMA升高相关。值得注意的是,许多关联在手术分娩的婴儿中比阴道分娩的婴儿更强。我们的研究结果表明,婴儿肠道微生物组中的砷代谢细菌与尿砷排泄之间存在关联。
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 log2-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 related KOs with >80% prevalence were log2-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 increased %MMA and %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.
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