人体肠道细菌广泛积累全氟辛烷磺酸

Anna E. Lindell, Anne Griesshammer, Lena Michaelis, Dimitrios Papagiannidis, Hannah Ochner, Stephan Kamrad, Rui Guan, Sonja Blasche, Leandro Ventimiglia, Bini Ramachandran, Hilal Ozgur, Aleksej Zelezniak, Nonantzin Beristain-Covarrubias, Juan Carlos Yam-Puc, Indra Roux, Leon P. Barron, Alexandra K. Richardson, Maria Guerra Martin, Vladimir Benes, Nobuhiro Morone, James Thaventhiran, Tanmay A.M. Bharat, Mikhail Savitski, Lisa Maier, Kiran Raosaheb Patil
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摘要

全氟烷基和多氟烷基物质(PFAS),即所谓的 "永远的化学品",由于其毒性和长期持久性[1,2],是引起环境和健康问题的主要原因。然而,目前尚未发现清除这些物质的有效机制。在此,我们报告了几种肠道细菌在从纳摩尔到 500 μM 的广泛浓度范围内对 PFAS 的生物累积作用。对于生物蓄积性极强的均匀乳杆菌(Bacteroides uniformis),我们估计其细胞内的 PFAS 浓度在毫摩尔范围内,高于大多数本地代谢物的浓度。尽管生物蓄积性很高,但在暴露于 250 μM 全氟壬酸(PFNA)的情况下,B. uniformis 细胞仍能正常生长。大肠杆菌对全氟辛烷磺酸的积累程度要低得多,但在缺乏 TolC 外排泵的情况下,大肠杆菌对全氟辛烷磺酸的生物蓄积性大大提高,这表明全氟辛烷磺酸的生物蓄积过程中存在跨膜转运。电子显微镜和低温聚焦离子束-二次离子质谱法显示了 PFNA 聚集体的明显形态变化和细胞内定位。蛋白质组学、代谢组学、热蛋白质组剖析以及实验室适应性进化后的突变也表明了全氟辛烷磺酸的生物累积和跨膜传输。在体内,与无菌对照组或定植了低生物蓄积细菌的小鼠相比,定植了人类肠道细菌的小鼠排泄粪便中的 PFNA 含量更高。由于肠道微生物群是暴露与人体之间的关键界面,我们的研究结果对了解和利用微生物对清除全氟辛烷磺酸的贡献具有重要意义。
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Extensive PFAS accumulation by human gut bacteria
Per- and polyfluoroalkyl Substances (PFAS) - the so-called 'forever chemicals' - are a major cause of environmental and health concern due to their toxicity and long-term persistence[1,2]. Yet, no efficient mechanisms for their removal have been identified. Here we report bioaccumulation of PFAS by several gut bacterial species over a wide range of concentrations from nanomolar up to 500 μM. For bioaccumulating Bacteroides uniformis, a highly prevalent species, we estimate intracellular PFAS concentration in the mM range - above that of most native metabolites. Despite this high bioaccumulation, B. uniformis cells could grow appreciably up to 250 μM perfluorononanoic acid (PFNA) exposure. Escherichia coli, which accumulated PFAS to a much lesser extent, substantially increased PFAS bioaccumulation when lacking TolC efflux pump indicating trans-membrane transport in PFAS bioaccumulation. Electron microscopy and cryogenic Focused Ion Beam-Secondary Ion Mass-spectrometry revealed distinct morphological changes and intracellular localisation of PFNA aggregates. Bioaccumulation of PFAS and transmembrane transport is also evident in proteomics, metabolomics, thermal proteome profiling, and mutations following adaptive laboratory evolution. In an in vivo context, mice colonized with human gut bacteria showed, compared to germ-free controls or those colonized with low-bioaccumulating bacteria, higher PFNA levels in excreted feces. As the gut microbiota is a critical interface between exposure and human body, our results have implications for understanding and utilizing microbial contribution to PFAS clearance.
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