Garcia Whitney L, Miller Carson J, Lomas Gerard X, Gaither Kari A, Tyrrell Kimberly J, Smith Jordan N, Brandvold Kristoffer R, Wright Aaron T
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, United States.
Biological Systems Engineering Department, CAHNRS, Washington State University, Pullman, Washington 99163, United States.
Chem Res Toxicol. 2022 Apr 18;35(4):585-596. doi: 10.1021/acs.chemrestox.1c00360. Epub 2022 Mar 29.
The gut microbiome is a key contributor to xenobiotic metabolism. Polycyclic aromatic hydrocarbons (PAHs) are an abundant class of environmental contaminants that have varying levels of carcinogenicity depending on their individual structures. Little is known about how the gut microbiome affects the rates of PAH metabolism. This study sought to determine the role that the gut microbiome has in determining the various aspects of metabolism in the liver, before and after exposure to two structurally different PAHs, benzo[]pyrene and 1-nitropyrene. Following exposures, the metabolic rates of PAH metabolism were measured, and activity-based protein profiling was performed. We observed differences in PAH metabolism rates between germ-free and conventional mice under both unexposed and exposed conditions. Our activity-based protein profiling (ABPP) analysis showed that, under unexposed conditions, there were only minor differences in total P450 activity in germ-free mice relative to conventional mice. However, we observed distinct activity profiles in response to corn oil vehicle and PAH treatment, primarily in the case of 1-NP treatment. This study revealed that the repertoire of active P450s in the liver is impacted by the presence of the gut microbiome, which modifies PAH metabolism in a substrate-specific fashion.
肠道微生物群是外源性物质代谢的关键贡献者。多环芳烃（PAHs）是一类丰富的环境污染物，根据其各自的结构具有不同程度的致癌性。关于肠道微生物群如何影响PAH代谢速率，人们知之甚少。本研究旨在确定肠道微生物群在接触两种结构不同的PAHs（苯并[a]芘和1-硝基芘）之前和之后，在决定肝脏代谢的各个方面所起的作用。接触后，测量PAH代谢的速率，并进行基于活性的蛋白质谱分析。我们观察到在未接触和接触条件下，无菌小鼠和常规小鼠之间PAH代谢速率存在差异。我们基于活性的蛋白质谱（ABPP）分析表明，在未接触条件下，无菌小鼠相对于常规小鼠的总P450活性只有微小差异。然而，我们观察到对玉米油载体和PAH处理有不同的活性谱，主要是在1-NP处理的情况下。这项研究表明，肝脏中活性P450的种类受到肠道微生物群的影响，肠道微生物群以底物特异性方式改变PAH代谢。
