Environmental Chemical Impact on the Host-Microbiome Interaction

项目总结/摘要 在环境健康科学和毒理学领域， 肠道微生物群在宿主对有毒化学品暴露的反应中的关键作用。已知微生物群 直接和间接影响饮食和环境化学品的毒性程度， 与多种疾病有关，包括代谢紊乱、癌症和炎性疾病。小心 通过严格的实验来确定微生物群影响环境的机制， 接触化学物质将使我们更全面地了解这些化学物质是如何破坏宿主的， 微生物群的相互作用，并将产生新的见解的关键信号通路的基础上， 干扰和不利的健康结果。重要的是，对微生物和环境化学物质的研究 可以提供关键的见解，更好地为可能对人类健康产生积极影响的风险评估提供信息。在这 R35 RIVER提案，我们计划在三个创新和互补的主题，以解决 统一的假设，即环境化学品暴露干扰宿主肠道微生物群的相互作用， 对健康有不利影响。首先，使用小鼠模型，我们将探索早期生活暴露于 环境化学品影响以后的生活健康结果（例如，急性和慢性代谢紊乱 炎症性肠病）通过宿主肠道微生物群轴的改变。第二，我们将研究如何 环境化学物质影响胃肠道的常见微生物，包括它们的 代谢活动和调节宿主生理的潜力。第三，我们将探索新的途径， 微生物群控制和宿主生理过程的影响。为了实现这些目标，我们组织了一个 多元化，协作，高度跨学科的团队，由生物化学，酶学， 免疫学、代谢、微生物学、转录调节和毒理学。帕特森实验室 在宿主肠道微生物群轴上沿着进行独特和开创性发现的历史，因此处于有利地位 凭借尖端的技术和方法，经验，创新的想法，以及开放/协作的 环境，以促进我们对宿主-肠道微生物群相互作用的理解，并帮助推动该领域的发展。 性新从翻译的角度来看，这些研究可能会导致新的保护方法，对饮食 以及通过设计新的益生元/益生菌的环境毒性。

PROJECT SUMMARY/ABSTRACT There is an increasing level of appreciation in the fields of environmental health sciences and toxicology on the critical role of the gut microbiota on the host response to toxic chemical exposure. The microbiota is known to directly and indirectly influence the extent of toxicity of dietary and environmental chemicals, and has been implicated in a wide-range of diseases including metabolic disorders, cancer, and inflammatory diseases. Careful and rigorous experimentation to determine the mechanism by which the microbiota influences environmental chemical exposure will lead to a more complete understanding of how these chemicals disrupt the host- microbiota interaction and will generate novel insights into the key signaling pathways underlying those perturbations and adverse health outcomes. Importantly, studies of the microbiota and environmental chemicals may provide key insights that will better inform risk assessment that could positively impact human health. In this R35 RIVER proposal, we plan to work across three innovative and complementary themes to address the unifying hypothesis that environmental chemical exposure perturbs the host-gut microbiota interaction to adversely affect health. First, using mouse models, we will explore the idea that early-life exposure to environmental chemicals impacts later life health outcomes (e.g., metabolic disorders, acute and chronic inflammatory bowel disorders) via alterations in the host-gut microbiota axis. Second, we will examine how environmental chemicals impact common commensal microbes of the gastrointestinal tract including their metabolic activities and potential to modulate host physiology. Third, we will explore new pathways involved in microbiota control and influence of host physiologic processes. To achieve these goals, we have assembled a diverse, collaborative, and highly interdisciplinary team consisting of experts in biochemistry, enzymology, immunology, metabolism, microbiology, transcriptional regulation, and toxicology. The Patterson lab has a long history of making unique and seminal discoveries along the host-gut microbiota axis and thus is well-positioned with cutting-edge technology and approaches, experience, innovative ideas, and an open/collaborative environment to advance our understanding of the host-gut microbiota interaction and help to move the field forward. From a translational standpoint, these studies may lead to new protective approaches toward dietary and environmental toxicity through design of new pre/probiotics.