Environmental Toxins and the Gut Microbiome

项目摘要 很明显，肠道微生物群显著影响人类健康，但关键的知识差距仍然存在于我们的 了解微生物在不同疾病状态下的功能。微生物进化出了一种巨大的 酶和代谢的多样性以生化方式转化环境毒素，并以生化方式 对至少一些有毒的外来生物化合物具有活性。然而，这些活动如何影响人类 健康，无论是积极的还是消极的，人们都知之甚少。人类面临着潜在的侮辱，范围从 对摄入受污染的食物和/或水的化学治疗药物(有时称为外源药物) 与有毒金属(LOID)S，可导致各种病理后遗症取决于剂量和时机 曝光。例如，砷已被美国环保局列为头号环境毒素 基于其在环境中的丰度和对人类健康的风险。据推测，肠道中的微生物 是第一批接受和转化有害化学物质的细胞，无论其来源如何，但结果和 这种暴露的后果在很大程度上是未知的。微生物组生物化学是否与毒素和/或 人工合成的对人体细胞有益的异类化合物？基础和临床的主要目标 研究人员将：1)确定肠道中重要的毒素生物化学；2)减轻有害毒素 微生物的生物转化，以及3)促进有益微生物群毒素的生物化学，以便更好地治疗 由环境暴露引起的疾病。

Project Summary It is clear that the gut microbiome significantly influences human health, but key knowledge gaps remain in our understanding of microbial function during various disease states. Microorganisms have evolved a great diversity of enzymes and metabolisms to biochemically transform environmental toxins, and are biochemically active against at least some toxic xenobiotic compounds. However, how these activities influence human health, positively or negatively, are poorly understood. Human exposure to potential insults, ranging from chemotherapeutics (sometimes referred to as xenobiotics) to the ingestion of food and/or water contaminated with toxic metal(loid)s, can result in a variety of pathologic sequelae depending on the dose and timing of exposure. For example, arsenic has been rated by the U.S.E.P.A. as the number one environmental toxin based on both its abundance in the environment and risk to human health. Presumably, microbes in the gut are among the first cells to receive and transform harmful chemicals, whatever the source, but outcomes and consequences of this exposure are largely unknown. Is microbiome biochemistry relating to toxins and/or synthetic xenobiotic compounds beneficial to human cells? Primary goals for both basic and clinical researchers are to: 1) identify important toxin biochemistry in the gut, 2) mitigate detrimental toxin biotransformations by microbes, and 3) promote beneficial microbiome toxin biochemistry so as to better treat diseases that arise from environmental exposures.