Laboratory of Experimental Toxicology - LATOEX, Universidade Federal de São Paulo, Instituto do Mar, Carvalho de Mendonça, 144, Santos, SP 11070-100, Brazil.
Department of Pharmacology, Universidade Federal de São Paulo - Escola Paulista de Medicina, Três de Maio, 100, São Paulo, SP 04044-020, Brazil.
Toxicology. 2024 Mar;503:153751. doi: 10.1016/j.tox.2024.153751. Epub 2024 Feb 13.
Environmental toxicants are chemical substances capable to impair environmental quality and exert adverse effects on humans and other animals. The main routes of exposure to these pollutants are through the respiratory tract, skin, and oral ingestion. When ingested orally, they will encounter trillions of microorganisms that live in a community - the gut microbiota (GM). While pollutants can disrupt the GM balance, GM plays an essential role in the metabolism and bioavailability of these chemical compounds. Under physiological conditions, strategies used by the GM for metabolism and/or excretion of xenobiotics include reductive and hydrolytic transformations, lyase and functional group transfer reactions, and enzyme-mediated functional transformations. Simultaneously, the host performs metabolic processes based mainly on conjugation, oxidation, and hydrolysis reactions. Thus, due to the broad variety of bacterial enzymes present in GM, the repertoire of microbial transformations of chemicals is considered a key component of the machinery involved in the metabolism of pollutants in humans and other mammals. Among pollutants, metals deserve special attention once contamination by metals is a worldwide problem, and their adverse effects can be observed even at very low concentrations due to their toxic properties. In this review, bidirectional interaction between lead, arsenic, cadmium, and mercury and the host organism and its GM will be discussed given the most recent literature, presenting an analysis of the ability of GM to alter the host organism's susceptibility to the toxic effects of heavy metals, as well as evaluating the extent to which interventions targeting the microbiota could be potential initiatives to mitigate the adverse effects resulting from poisoning by heavy metals. This study is the first to highlight the overlap between some of the bacteria found to be altered by metal exposure and the bacteria that also aid the host organism in the metabolism of these metals. This could be a key factor to determine the beneficial species able to minimize the toxicity of metals in future therapeutic approaches.
环境毒物是指能够损害环境质量并对人类和其他动物产生不利影响的化学物质。这些污染物的主要暴露途径是通过呼吸道、皮肤和口服摄入。当经口摄入时，它们将遇到生活在一个群落中的数万亿种微生物 - 肠道微生物群（GM）。虽然污染物可以破坏 GM 平衡，但 GM 在这些化学化合物的代谢和生物利用度方面起着至关重要的作用。在生理条件下，GM 用于代谢和/或排泄外来化合物的策略包括还原和水解转化、裂合酶和功能基团转移反应以及酶介导的功能转化。同时，宿主主要基于结合、氧化和水解反应进行代谢过程。因此，由于 GM 中存在广泛的细菌酶，微生物对化学物质的转化谱被认为是涉及人类和其他哺乳动物中污染物代谢的机制的关键组成部分。在污染物中，金属特别值得关注，因为金属污染是一个全球性问题，由于其毒性，即使在非常低的浓度下也可以观察到它们的不利影响。在本综述中，根据最新文献讨论了铅、砷、镉和汞与宿主生物体及其 GM 之间的双向相互作用，分析了 GM 改变宿主生物体对重金属毒性作用的易感性的能力，并评估了针对微生物组的干预措施在多大程度上可以成为减轻重金属中毒不良影响的潜在举措。这项研究首次强调了一些因金属暴露而发生改变的细菌与那些也有助于宿主生物体代谢这些金属的细菌之间的重叠。这可能是确定能够在未来治疗方法中最大限度地减少金属毒性的有益物种的关键因素。
