Toxicology Department, National Institute for Occupational Health (a division of the National Health Laboratory Service), Johannesburg, 2000, South Africa; Department of Environmental Heath, Faculty of Health Sciences, University of Johannesburg, Johannesburg, 2000, South Africa.
Department of Biomedical Sciences, College of Medicine, University Of Malawi, Blantyre, Malawi; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Chemosphere. 2021 May;271:129817. doi: 10.1016/j.chemosphere.2021.129817. Epub 2021 Jan 29.
Many in vivo and in vitro studies have shown that pesticides can disrupt the functioning of gut microbiota (GM), which can lead to many diseases in humans. While the tests developed by the Organization of Economic Cooperation and Development (OECD) are expected to capture most apical effects resulting from GM disruptions, exclusion of GM in the risk assessment might mischaracterize hazards or overestimate/underestimate risks, especially when extrapolating results from one species to another species or population with a substantially different GM. On the other hand, direct assessment of GM-mediated effects may face challenges in identifying hazards, since not all GM perturbations will lead to human adverse effects. In this regard, reliable and validated biomarkers for common GM-mediated adverse effects may be very useful in the identification of GM-mediated pesticide toxicity. Nevertheless, proving causality of GM-mediated effects will need modifications of Bradford Hill criteria as well as Koch's postulates, which are more suitable for the "one-pathogen" paradigm. Furthermore, risk assessment of GM-mediated effects may require pesticide toxicokinetics along the gut, possibly through modeling, and the establishment of the involvement of GM in the mechanism of action (MOA) of the pesticide. Risk assessment of GM mediated effects also requires the standardization of experimental approaches as well as the establishment of microbial reference communities, since variations exist among GM in human populations.
许多体内和体外研究表明，农药会破坏肠道微生物组（GM）的功能，这可能导致人类患上许多疾病。虽然经济合作与发展组织（OECD）开发的测试预计将捕捉到由于 GM 破坏而导致的大多数顶端效应，但在风险评估中排除 GM 可能会错误地描述危害或高估/低估风险，尤其是在将结果从一个物种推断到另一个具有明显不同 GM 的物种或人群时。另一方面，直接评估 GM 介导的效应可能在识别危害方面面临挑战，因为并非所有 GM 扰动都会导致人类不良反应。在这方面，用于常见 GM 介导的不良反应的可靠和经过验证的生物标志物可能对于识别 GM 介导的农药毒性非常有用。然而，要证明 GM 介导的效应的因果关系，需要对 Bradford Hill 标准和 Koch 的假设进行修改，这些标准更适合“单病原体”范式。此外，GM 介导的效应的风险评估可能需要沿肠道进行农药毒代动力学研究，可能需要通过建模来进行，并且需要确定 GM 参与农药作用机制（MOA）。GM 介导的效应的风险评估还需要标准化实验方法并建立微生物参考群落，因为人群中的 GM 存在差异。
