Functional interaction between the gut microbiome and arsenic exposure

 描述(由首席调查员提供)：在理解环境暴露-肠道微生物群相互作用在影响人类健康方面的作用方面存在着根本的差距。人体肠道微生物群通过其在与宿主相关的广泛功能中的关键作用，对人类健康产生深远的影响。接触无机砷(IAS)是世界范围内一个重要的公共卫生问题，并与许多疾病有关，包括癌症、代谢障碍、心血管疾病和免疫功能受损。越来越多的证据表明，肠道微生物区系失调对其中许多疾病有重要作用，这突显了肠道微生物群在砷诱导的疾病中可能发挥的重要作用。然而，除了研究人员最近的研究外，肠道微生物群和砷暴露之间的功能相互作用在很大程度上还没有被探索。他们的中心假设是肠道微生物群-砷的相互作用影响了IAS的毒性。这一假设是在首席调查员实验室产生的令人兴奋的初步数据的基础上提出的，并将通过追求三个具体目标进行检验，包括 目的是明确IAS对肠道微生物群落及其功能的影响，并阐明肠道微生物群落结构在介导砷中毒中的作用。这项拨款申请的意义在于，尽管肠道微生物群在人类健康中具有广泛而深刻的作用，但肠道微生物群与暴露之间的相互作用在很大程度上仍未得到探索。研究人员提出的研究也具有很高的创新性，代表了毒理学的范式转变，因为他们专注于肠道微生物群扰动，认为这是暴露诱导疾病的一种新机制，也是导致个人易感性的未知风险因素。这项赠款申请的创新还源于集成生物分析和计算工具的新应用，以系统水平研究重要的肠道微生物群-暴露相互作用。这项研究的结果有望为未来的研究奠定基础，这些研究旨在扩大我们对暴露于IAS导致或加剧人类疾病的新机制的理解：微生物组的作用。

 DESCRIPTION (provided by Principal Investigator): There is a fundamental gap in understanding the role of environmental exposure-gut microbiome interactions in affecting human health. The microbiome of the human intestinal tract has a profound effect on human health through its key role in a wide range of host-related functions. Exposure to inorganic arsenic (iAs) is a significant public health issue worldwide and has been linked to a number of diseases, including cancers, metabolic disorders, cardiovascular diseases and impaired immune functions. Mounting evidence indicates that dysregulated gut microflora contribute significantly to many of these diseases, underscoring a potentially important role of the gut microbiome in arsenic-induced diseases. However, functional interaction between the gut microbiome and arsenic exposure is largely unexplored, except for the investigators' recent studies. Their central hypothesis is that the gut microbiome-arsenic interaction influences iAs toxicity. This hypothesis has been formulated on the basis of exciting preliminary data produced in the Principal Investigator's laboratory and will be tested by pursuing three specific aims, with the goal of defining the effects of iAs on the gut microbiome and its function and elucidating the role of gut microbiome community structures in mediating arsenic toxicity. The significance of this grant application lies in the fact that gut microbiome-exposure interaction is still largely unexplored despite the diverse and profound roles of the microbiome in human health. The investigators' proposed studies are also highly innovative and represent a paradigm shift in toxicology because they focus on gut microbiome perturbations as a novel mechanism of exposure-induced diseases and an unexplored risk factor responsible for individual susceptibility. The innovation of this grant application also stems from the novel application of integrated bioanalytical and computational tools to a systems-level study of a significant gut microbiome-exposure interaction. Findings from this study are expected to lay a foundation for future studies aiming at expanding our understanding of new mechanisms by which exposure to iAs leads to or exacerbates human disease: the role of the microbiome.