Functional interaction between the gut microbiome and arsenic exposure

 描述（由主要研究者提供）：在理解环境微生物-肠道微生物组相互作用在影响人类健康方面的作用方面存在根本性的差距。人类肠道的微生物组通过其在广泛的宿主相关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）是全球范围内的一个重大公共卫生问题，并与许多疾病有关，包括癌症、代谢紊乱、心血管疾病和免疫功能受损。越来越多的证据表明，肠道菌群失调对许多这些疾病有重要作用，强调了肠道微生物组在砷引起的疾病中的潜在重要作用。然而，肠道微生物组和砷暴露之间的功能性相互作用在很大程度上尚未探索，除了研究人员最近的研究。他们的核心假设是肠道微生物组-砷相互作用影响iAs毒性。这一假设是在主要研究者实验室产生的令人兴奋的初步数据的基础上制定的，并将通过追求三个具体目标进行测试， 目标是确定iAs对肠道微生物组及其功能的影响，并阐明肠道微生物组群落结构在介导砷毒性中的作用。这项拨款申请的重要性在于，尽管微生物组在人类健康中发挥着多种多样和深远的作用，但肠道微生物组与暴露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高度创新性，代表了毒理学的范式转变，因为他们专注于肠道微生物组扰动作为一种新的应激诱导疾病机制，以及一种未探索的导致个体易感性的风险因素。这项资助申请的创新还源于将综合生物分析和计算工具应用于对肠道微生物组暴露相互作用的系统级研究。这项研究的结果有望为未来的研究奠定基础，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.