Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
Int J Mol Sci. 2022 Jul 26;23(15):8220. doi: 10.3390/ijms23158220.
Early life exposure to environmental pollutants may have long-term consequences and harmful impacts on health later in life. Here, we investigated the short- and long-term impact of early life 3,3',4,4',5-pentacholorobiphenyl (PCB 126) exposure (24 μg/kg body weight for five days) in mice on the host and gut microbiota using 16S rRNA gene sequencing, metagenomics, and H NMR- and mass spectrometry-based metabolomics. Induction of , an aryl hydrocarbon receptor (AHR)-responsive gene, was observed at 6 days and 13 weeks after PCB 126 exposure consistent with the long half-life of PCB 126. Early life, Short-Term PCB 126 exposure resulted in metabolic abnormalities in adulthood including changes in liver amino acid and nucleotide metabolism as well as bile acid metabolism and increased hepatic lipogenesis. Interestingly, early life PCB 126 exposure had a greater impact on bacteria in adulthood at the community structure, metabolic, and functional levels. This study provides evidence for an association between early life environmental pollutant exposure and increased risk of metabolic disorders later in life and suggests the microbiome is a key target of environmental chemical exposure.
早期生活环境污染物暴露可能对以后的健康产生长期影响和有害影响。在这里，我们使用 16S rRNA 基因测序、宏基因组学以及基于 H NMR 和质谱的代谢组学研究了早期生活中 3,3',4,4',5-五氯联苯（PCB 126）暴露（24μg/kg 体重，持续 5 天）对宿主和肠道微生物群的短期和长期影响。在 PCB 126 暴露后 6 天和 13 周观察到芳基烃受体（AHR）反应基因的诱导，这与 PCB 126 的长半衰期一致。早期生活，短期 PCB 126 暴露导致成年期代谢异常，包括肝脏氨基酸和核苷酸代谢以及胆汁酸代谢的变化以及肝内脂肪生成增加。有趣的是，早期生活 PCB 126 暴露对成年期细菌的群落结构、代谢和功能水平产生了更大的影响。这项研究为早期生活环境污染物暴露与以后生活中代谢紊乱风险增加之间的关联提供了证据，并表明微生物组是环境化学暴露的关键靶点。
